A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.
Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.
Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.
A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.
Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.
A family of hexahydropyridines.
Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers.
OXAZINES with a fused BENZENE ring.
Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.
Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.
Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.
GLYCEROL esterified with FATTY ACIDS.
Compound isolated from Cannabis sativa extract.
Phenomena and pharmaceutics of compounds that bind to the same receptor binding-site as an agonist (DRUG AGONISM) for that receptor but exerts the opposite pharmacological effect.
A physiologically inactive constituent of Cannabis sativa L.
An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.
The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.
Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality.
Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.
The observable response an animal makes to any situation.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A group of compounds that are derivatives of methoxybenzene and contain the general formula R-C7H7O.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)
Lower than normal body temperature, especially in warm-blooded animals.
Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.
A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents).
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
The physical activity of a human or an animal as a behavioral phenomenon.
Organic esters or salts of sulfonic acid derivatives containing an aliphatic hydrocarbon radical.
Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.
The motor activity of the GASTROINTESTINAL TRACT.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The strengthening of a conditioned response.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.
A group of 16-carbon fatty acids that contain no double bonds.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure.
The consumption of edible substances.
Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.
A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
Amount of stimulation required before the sensation of pain is experienced.
Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.
The most common inhibitory neurotransmitter in the central nervous system.
Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Elements of limited time intervals, contributing to particular results or situations.
Use of electric potential or currents to elicit biological responses.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
BENZOIC ACID amides.
A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning.
An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.
A general term referring to the learning of some particular response.
The function of opposing or restraining the excitation of neurons or their target excitable cells.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin.
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Established cell cultures that have the potential to propagate indefinitely.
Inhaling and exhaling the smoke from CANNABIS.
Purine bases found in body tissues and fluids and in some plants.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.

A critical role for the cannabinoid CB1 receptors in alcohol dependence and stress-stimulated ethanol drinking. (1/1474)

Although many people drink alcohol regularly, only some become addicted. Several studies have shown that genetic and environmental factors contribute to individual differences in the vulnerability to the effects of alcohol (Nestler, 2000; Kreek, 2001; Crabbe, 2002). Among the environmental factors, stress is perhaps the most important trigger for relapse after a period of abstinence (Koob and Nestler, 1997; Piazza and Le Moal, 1998; Koob and Le Moal, 2001; Weiss et al., 2001). Here we show that ethanol withdrawal symptoms were completely absent in cannabinoid CB1 receptor-deficient mice, although acute effects of ethanol and ethanol tolerance and preference were basically normal. Furthermore, foot-shock stress had no affect on alcohol preference in Cnr1-/- mice, although it induced a dramatic increase in Cnr1+/+ animals. These results reveal a critical role for the CB1 receptor in clinically important aspects of alcohol dependence and provide a rationale for the use of CB1 receptor antagonists in the treatment of alcohol addiction.  (+info)

Cannabinoid CB(1) receptor-mediated inhibition of hippocampal acetylcholine release is preserved in aged mice. (2/1474)

1. The cannabinoid CB(1) receptor inverse agonist/antagonist SR 141716 increases acetylcholine release in rodent hippocampus and improves memory in some experimental paradigms. Since drugs like SR 141716 may represent a novel class of cognition-enhancing drugs, we wanted to check whether the function of the CB(1) receptor is preserved during ageing. 2. Hippocampal and striatal slices from 2- to 3- and 24- to 28-month-old C57BL/6J mice were preincubated with [(3)H]-choline or [(3)H]-noradrenaline ([(3)H]-NA) and superfused. 3. The cannabinoid receptor agonist WIN 55212-2 inhibited, and SR 141716 facilitated, the electrically (3 Hz) evoked tritium overflow in hippocampal slices (preincubated with [(3)H]-choline) from young and aged mice to the same extent. The evoked overflow per se was less by 33% in slices from aged animals. 4. WIN 55212-2 and SR 141716 did not affect, but the muscarinic receptor agonist oxotremorine inhibited, the evoked (3 Hz) overflow in striatal slices (preincubated with [(3)H]-choline) from young and aged mice to the same extent. The evoked overflow per se tended to be less in slices from aged animals. 5. The evoked (0.3 Hz) overflow in hippocampal slices (preincubated with [(3)H]-NA) was not affected by WIN 55212-2 and SR 141716, but was inhibited by histamine (via H(3) receptors) in slices from young mice and, to a somewhat less extent, in slices from aged mice. The evoked overflow per se did not differ between age groups. 6. In conclusion, the function of the CB(1) receptor involved in the tonic inhibition of hippocampal acetylcholine release is preserved in aged mice.  (+info)

A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling pathway. (3/1474)

(1) We examined A3 adenosine and CB1 cannabinoid receptor-coupled signaling pathways regulating Cl(-) current in a human nonpigmented ciliary epithelial (NPCE) cell line. (2) Whole-cell patch-clamp recordings demonstrated that the A3 receptor agonist, IB-MECA, activates an outwardly rectifying Cl(-)current (I(Cl,Aden)) in NPCE cells, which was inhibited by the adenosine receptor antagonist, CGS-15943 or by the protein kinase C (PKC) activator, phorbol 12,13 dibutyrate (PDBu). (3) Treatment of NPCE cells with pertussis-toxin (PTX), or transfection with the COOH-terminus of beta-adrenergic receptor kinase (ct-betaARK), inhibited I(Cl,Aden). The phosphatidyl inositol 3-kinase (PI3K) inhibitor, wortmannin, had no effect on I(Cl,Aden); however, the mitogen-activated protein kinase kinase (MEK) inhibitor, PD98059, inhibited I(Cl,Aden). (4) Reverse transcription-polymerase chain reaction experiments and immunocytochemistry confirmed mRNA and protein expression for the CB1 receptor in NPCE cells, and the CB1 receptor agonist, Win 55,212-2, activated a PDBu-sensitive Cl(-) current (I(Cl,Win)). (5) Transfection of NPCE cells with the human CB1 (hCB1) receptor, increased I(Cl,Win), consistent with increased receptor expression, and I(Cl,Win) in hCB1 receptor-transfected cells was decreased after application of a CB1 receptor inverse agonist, SR 141716. (6) Constitutive activity for CB1 receptors was not significant in NPCE cells as transfection with hCB1 receptors did not increase basal Cl(-) current, nor was basal current inhibited by SR 141716. (7) I(Cl,Win) was inhibited by PTX preincubation, by transfection with ct-betaARK and by the MEK inhibitor, PD98059, but unaffected by the PI3K inhibitor, wortmannin. (8) We conclude that both A3 and CB1 receptors activate a PKC-sensitive Cl(-) current in human NPCE cells via a G(i/o)/Gbetagamma signaling pathway, in a manner independent of PI3K but involving MAPK.  (+info)

Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. (4/1474)

1 Two cannabinoid receptors, CB1 and CB2, have been identified. The CB1 receptor is preferentially expressed in brain, and the CB2 receptor in cells of leukocyte lineage. We identified the mRNA for the CB1 receptor in human neuroblastoma SH-SY5Y cells, and the mRNA and protein for the CB2 receptor in human microglia and THP-1 cells. 2 Delta(9)-and Delta(8)-tetrahydrocannabinol (THC) were toxic when added directly to SH-SY5Y neuroblastoma cells. The toxicity of Delta(9)- THC was inhibited by the CB1 receptor antagonist SR141716A but not by the CB2 receptor antagonist SR144528. The endogenous ligand anandamide was also toxic, and this toxicity was enhanced by inhibitors of its enzymatic hydrolysis. 3 The selective CB2 receptor ligands JWH-015 and indomethacin morpholinylamide (BML-190), when added to THP-1 cells before stimulation with lipopolysaccharide (LPS) and IFN-gamma, reduced the toxicity of their culture supernatants to SH-SY5Y cells. JWH-015 was more effective against neurotoxicity of human microglia than THP-1 cells. The antineurotoxic activity of JWH-015 was blocked by the selective CB2 receptor antagonist SR144528, but not by the CB1 receptor antagonist SR141716A. This activity of JWH-015 was synergistic with that of the 5-lipoxygenase (5-LOX) inhibitor REV 5901. 4 Cannabinoids inhibited secretion of IL-1beta and tumor necrosis factor-alpha (TNF-alpha) by stimulated THP-1 cells, but these effects could not be directly correlated with their antineurotoxic activity. 5 Specific CB2 receptor ligands could be useful anti-inflammatory agents, while avoiding the neurotoxic and psychoactive effects of CB1 receptor ligands such as Delta(9)-THC.  (+info)

Cannabinoid1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets. (5/1474)

Delta9-tetrahydrocannabinol (delta9-THC) is an effective anti-emetic; however, other potential gastrointestinal therapeutic effects of delta9-THC are less well-known. Here, we report a role of delta9-THC in a vago-vagal reflex that can result in gastro-oesophageal reflux, that is, gastric distension-evoked lower oesophageal sphincter (LOS) relaxation. Oesophageal, LOS and gastric pressures were measured using a miniaturized, manometric assembly in decerebrate, unanaesthetized ferrets.Gastric distension (30 ml) evoked LOS relaxation (70 +/- 8% decrease from baseline). Delta9-THC administered systemically (0.2 mg kg-1, iv.) or directly to the dorsal hindbrain surface (0.002 mg),significantly attenuated the nadir of the gastric distention-evoked LOS relaxation, and time to reach maximal response. Similar increases to maximal effect were observed after treatment with the cannabinoid receptor agonist WIN 55,212-2 (0.2 mg kg-1 iv.). The effect of systemic delta9-THC on gastric distention-evoked LOS relaxation was reversed by a selective cannabinoid1 (CBI) receptor antagonist, SR141617A (1 mg kg-1 i.v.). Since this reflex is vagally mediated, we used a CB1 receptor antiserum and immunocytochemistry to determine its distribution in ferret vagal circuitry. CBI receptor staining was present in cell bodies within the area postrema, nucleus tractus solitarius (NTS) and nodose ganglion. Intense terminal-like staining was noted within the NTS and dorsal motor vagal nucleus (DMN). Neither nodose ganglionectomy nor vagotomy altered the CB1 receptor terminal-like staining in the dorsal vagal complex. Retrogradely labelled gastric- or LOS-projecting DMN neurones did not express CBI receptors within their soma. Therefore, CBI receptor staining in the NTS and DMN is not due to primary vagal afferents or preganglionic neurones. These novel findings suggest that delta9-THC can modulate reflex LOS function and that the most likely site of action is via the CBI receptor within the NTS. This effect of delta9-THC may have implications in treatment of gastro-oesophageal reflux and other upper gut disorders.  (+info)

Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission in mouse colon. (6/1474)

The effects of cannabinoid receptor agonists and antagonists on smooth muscle resting membrane potentials and on membrane potentials following electrical neuronal stimulation in a myenteric neuron/smooth muscle preparation of wild-type and cannabinoid receptor type 1 (CB1)-deficient mice were investigated in vitro. Double staining for CB1 and nitric oxide synthase (neuronal) was performed to identify the myenteric CB1-expressing neurons. Focal electrical stimulation of the myenteric plexus induced a fast (f) excitatory junction potential (EJP) followed by a fast and a slow (s) inhibitory junction potential (IJP). Treatment of wild-type mice with the endogenous CB1 receptor agonist anandamide reduced EJP while not affecting fIJP and sIJP. EJP was significantly higher in CB1-deficient mice than in wild-type littermate controls, and anandamide induced no effects in CB1-deficient mice. N-arachidonoyl ethanolamide (anandamide), R-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]- 1,4-benzoxazin-6-yl]-1-naphtalenylmethanone, a synthetic CB1 receptor agonist, nearly abolished EJP and significantly reduced the fIJP in wild-type mice. N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-caroxa mide (SR141716A), a CB1-specific receptor antagonist, was able to reverse the agonist effects induced in wild-type mice. SR141716A, when given alone, significantly increased EJP in wild-type mice without affecting IJP in wild-type and EJP in CB1-deficient mice. Interestingly, SR141716A reduced fIJP in CB1-deficient mice. In the mouse colon, nitrergic myenteric neurons do not express CB1, implying that CB1 is expressed in cholinergic neurons, which is in line with the functional data. Finally, excitatory and inhibitory neurotransmission in the mouse colon is modulated by activation of CB1 receptors. The significant increase in EJP in CB1-deficient mice strongly suggests a physiological involvement of CB1 in excitatory cholinergic neurotransmission.  (+info)

Toxicological and structural features of organophosphorus and organosulfur cannabinoid CB1 receptor ligands. (7/1474)

Potent cannabinoid CB1 receptor ligands include anandamide [N-(2-hydroxyethyl)arachidonamide], Delta9-tetrahydrocannabinol, and 3H-CP 55,940 at the agonist site and selected organophosphorus esters (including some pesticides) and organosulfur compounds at a proposed closely coupled "nucleophilic" site. This study considers the toxicological and structural features of alkylfluorophosphonates, benzodioxaphosphorin oxides, alkanesulfonyl fluorides, and analogs acting at the nucleophilic site. Binding at the agonist site, using3H-CP 55,940 in assays with mouse brain membranes, is inhibited byO-isopropyl dodecylfluorophosphonate (compound 2), dodecanesulfonyl fluoride (compound 14) and dodecylbenzodioxaphosphorin oxide with IC50 values of 2-11 nM. Compounds 2 and 14 are also effectivein vivo, with 84% inhibition of mouse brain CB1 binding 4 h after intraperitoneal dosage at 30 mg/kg. Compound 14-inhibited CB1 in mouse brain requires about 3-4 days for recovery of 50% activity, suggesting covalent derivatization. Delayed toxicity (mortality in 0.3-5 days) from compounds 2, 14, and octanesulfonyl fluoride (18) is more closely associated with in vivo inhibition of brain neuropathy target esterase-lysophospholipase (NTE-LysoPLA) than with that of CB1 or acetylcholinesterase. NTE-LysoPLA inhibited by sulfonyl fluorides 14 and 18 cannot "age," a proposed requirement for NTE phosphorylated by organophosphorus-delayed neurotoxicants. Several octane- and dodecanesulfonamides with N-(2-hydroxyethyl) and other substituents based on anandamide give depressed mobility and recumbent posture in mice, but the effects do not correlate with potency for CB1 inhibition in vitro. Specific toxicological responses are not clearly associated with organophosphorus- or organosulfur-induced inhibition of the proposed CB1 nucleophilic site in mouse brain. On the other hand, the most potent CB1 inhibitors examined here are also NTE-LysoPLA inhibitors and cause delayed toxicity in mice.  (+info)

The cannabinoid system and immune modulation. (8/1474)

Studies on the effects of marijuana smoking have evolved into the discovery and description of the endocannabinoid system. To date, this system is composed of two receptors, CB1 and CB2, and endogenous ligands including anandamide, 2-arachidonoyl glycerol, and others. CB1 receptors and ligands are found in the brain as well as immune and other peripheral tissues. Conversely, CB2 receptors and ligands are found primarily in the periphery, especially in immune cells. Cannabinoid receptors are G protein-coupled receptors, and they have been linked to signaling pathways and gene activities in common with this receptor family. In addition, cannabinoids have been shown to modulate a variety of immune cell functions in humans and animals and more recently, have been shown to modulate T helper cell development, chemotaxis, and tumor development. Many of these drug effects occur through cannabinoid receptor signaling mechanisms and the modulation of cytokines and other gene products. It appears the immunocannabinoid system is involved in regulating the brain-immune axis and might be exploited in future therapies for chronic diseases and immune deficiency.  (+info)

The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol, the active agent in cannabis, and other phytocannabinoids (plant cannabinoids). The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG). CB2 was cloned in 1993 by a research group from Cambridge looking for a second cannabinoid receptor that could explain the pharmacological properties of tetrahydrocannabinol. The receptor was identified among cDNAs based on its similarity in amino-acid sequence to the cannabinoid receptor type 1 (CB1) receptor, discovered in 1990. The discovery of this receptor helped provide a molecular explanation for the established effects of cannabinoids on the immune system. ...
We document in vitro and in vivo effects of a novel, selective cannabinoid CB(1) receptor inverse agonist, Imidazole 24b (5-(4-chlorophenyl)-N-cyclohexyl-4-(2,4-dichlorophenyl)-1-methyl-imidazole-2-carboxamide). The in vitro binding affinity of Imidazole 24b for recombinant human and rat CB(1) receptor is 4 and 10 nM, respectively. Imidazole 24b binds to human cannabinoid CB(2) receptor with an affinity of 297 nM; in vitro, it is a receptor inverse agonist at both cannabinoid CB(1) and CB(2) receptors as it causes a further increase of forskolin-induced cAMP increase. Oral administration of Imidazole 24b blocked CP-55940-induced hypothermia, demonstrating cannabinoid CB(1) receptor antagonist efficacy in vivo. Using ex vivo autoradiography, Imidazole 24b resulted in dose-dependent increases in brain cannabinoid CB(1) receptor occupancy (RO) at 2h post-dosing in rats, indicating that approximately 50% receptor occupancy is sufficient for attenuation of receptor agonist-induced hypothermia. ...
The endocannabinoid system regulates food intake, energy, and glucose metabolism at both central and peripheral levels. We have investigated the mechanism by which it may control glucose uptake in skeletal muscle cells. Detectable levels of the cannabinoid receptor type 1 (CB1) were revealed in L6 cells. Exposure of differentiated L6 myotubes to the CB1 antagonist rimonabant (SR141716) selectively increased 2-deoxyglucose uptake (2-DG) in a time- and dose-dependent manner. A similar effect was induced by genetic silencing of CB1 by small interfering RNA. Protein expression profiling revealed that both the regulatory p85 and the catalytic p110 subunits of the phosphatidylinositol-3-kinase (PI3K) were increased by SR141716. No significant change in the cellular content of other known molecules regulating PI3K was observed. However, phosphoinositide-dependent kinase-1, Akt/protein kinase B, and protein kinase Cζ activities were rapidly induced after SR141716 treatment of L6 cells in a ...
The endocannabinoid system possesses neuromodulatory functions by influencing the release of various neurotransmitters, including γ-aminobutyric acid (GABA) and glutamate. A functional interaction between endocannabinoids and the serotonergic system has already been suggested. Previously, we showed that cannabinoid type 1 (CB1) receptor mRNA and protein are localized in serotonergic neurons of the raphe nuclei, implying that the endocannabinoid system can modulate serotonergic functions. In order to substantiate the physiological role of the CB1 receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic (5-HT) neuron-specific CB1 receptor-deficient mice, using the Cre/loxP system with a tamoxifen-inducible Cre recombinase under the control of the regulatory sequences of the tryptophan hydroxylase 2 gene (TPH2-CreERT2), thus, restricting the recombination to 5-HT neurons of the central nervous system. Applying several different behavioral paradigms, we revealed that mice lacking the
Title:Latest Progress in the Identification of Novel Synthetic Ligands for the Cannabinoid CB2 Receptor. VOLUME: 14 ISSUE: 5. Author(s):Shuang Han, Jiong-Jiong Chen and Jian-Zhong Chen. Affiliation:College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, P. R. China.. Keywords:Cannabinoid receptors, CB2, GPCRs, selective ligand, structure-activity relationship.. Abstract:Cannabinoid receptors, belonging to the superfamily of G-protein coupled receptors, play a major role in pathophysiology of a wide range of disparate diseases. Cannabinoid CB2 receptor, which mainly locates in peripheral tissues, represents as a promising drug target for the treatment of pain, osteoporosis, liver disorders, and so on without serious CNS side effects. In the past decades, the identification and optimization of selective ligands for the CB2 receptor has been a major objective in drug discovery. In the present review, we describe recent advances in the development of ...
TY - PAT. T1 - 1,5-diaryl-pyrazoles as cannabinoid receptor neutral antagonists useful as therapeutic agents. AU - Greig, Iain Robert. AU - Ross, Ruth Alexandra. AU - Pertwee, Roger Guy. PY - 2008/8/21. Y1 - 2008/8/21. N2 - The present invention pertains to cannabinoid (CB) receptor neutral antagonists, and especially CB1 neutral antagonists, and including, for example, certain 1,5-di-aryl-pyrazole compounds. The present invention also pertains to the use of such compounds in the treatment of diseases and disorders that are ameliorated by treatment with a neutral antagonist of the cannabinoid type 1 (CB1) receptor, for example: an eating disorder; obesity; a disease or disorder characterised by an addiction component; addiction; withdrawal; smoking addiction; smoking withdrawal; drug addiction; drug withdrawal; smoking cessation therapy; a bone disease or disorder; osteoporosis, Pagets disease of bone; bone related cancer; a disease or disorder with an inflammatory or autoimmune component; ...
This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
Abstract: The endocannabinoid system has been historically targeted for medicinal purposes through the use of cannabis. Two cannabinoid receptors, CB1 and CB2, have been identified as the mediators of the biological effects of the main psychoactive component in Cannabis sativa; delta-9-tetrahydrocannabinol. The CB1 receptor is a class A G-protein coupled receptor (GPCR), and is the most abundant neuro-modulatory receptor in the CNS. With its location at presynaptic termini, it regulates the function of other receptors, including the dopamine, serotonin, GABA, opioid and glutamate receptors. Many potential therapeutic applications targeting the CB1 receptor are under investigation. However, the unformed knowledge in drug-receptor interactions at the molecular level, and in the CB1 receptor signaling properties, has hampered the transition of many synthesized CB1 receptor agonists and antagonists to clinical use. In the studies to be presented, computational and mutational methods are employed to ...
TY - JOUR. T1 - Brain Cannabinoid CB2 Receptor in Schizophrenia. AU - Ishiguro, Hiroki. AU - Horiuchi, Yasue. AU - Ishikawa, Maya. AU - Koga, Minori. AU - Imai, Keiko. AU - Suzuki, Yoshimi. AU - Morikawa, Miyuki. AU - Inada, Toshiya. AU - Watanabe, Yuichiro. AU - Takahashi, Makoto. AU - Someya, Toshiyuki. AU - Ujike, Hiroshi. AU - Iwata, Nakao. AU - Ozaki, Norio. AU - Onaivi, Emmanuel S.. AU - Kunugi, Hiroshi. AU - Sasaki, Tsukasa. AU - Itokawa, Masanari. AU - Arai, Makoto. AU - Niizato, Kazuhiro. AU - Iritani, Shyuji. AU - Naka, Izumi. AU - Ohashi, Jun. AU - Kakita, Akiyoshi. AU - Takahashi, Hitoshi. AU - Nawa, Hiroyuki. AU - Arinami, Tadao. PY - 2010/5/15. Y1 - 2010/5/15. N2 - Background: Neural endocannabinoid function appears to be involved in schizophrenia. Two endocannabinoid receptors, CB1 and CB2, are found in the brain and elsewhere in the body. We investigated roles of CB2 in schizophrenia. Materials and Methods: An association study was performed between tag single nucleotide ...
TY - JOUR. T1 - CB1 cannabinoid receptor induction in experimental stroke. AU - Jin, Kun Lin. AU - Mao, Xiao Ou. AU - Goldsmith, Paul C.. AU - Greenberg, David A.. PY - 2000. Y1 - 2000. N2 - Cannabinoids protect cortical neurons from ischemic injury by interacting with CB1 receptors. Because a variety of neuroprotective genes are induced in cerebral ischemia, we examined the effect of experimental stroke, produced by 20 minutes of middle cerebral artery occlusion in rats, on CB1 receptor expression. Western blotting and immunohistochemistry showed that CB1 expression on neurons was increased in the arterial boundary zone of the cortical mantle, beginning by 2 hours and persisting for 72 hours or more after ischemia. These findings are consistent with a neuroprotective role for endogenous cannabinoid signaling pathways and with a potential therapeutic role in stroke for drugs that activate CB1 receptors.. AB - Cannabinoids protect cortical neurons from ischemic injury by interacting with CB1 ...
© 2014 The Authors. The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50 <200nM) and binding affinity (K i <200nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases.
Mediterranean Yearbook (Med) is a full-text scholarly ejournal. The bulk of the articles here are not relevant to the arts and humanities, but there are occasional themed sections on cultural and media issues. Of particular note is the themed section The Role of the Media in the Mediterranean (four articles in the 2003/2004 issue). Other articles of interest include: Summer Festivals in Morocco: International Influence and a Factor of Social Cohesion; The Influence of Arab Information C ...
Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well
With Sativex approved in a number of countries and expected to find approval in many more in the coming months, the concept of cannabinoid medicine has been proved as more than a kooky herbal remedy. The Sativex approval has validated the platform; it says you can make a medicine out of these materials and in this way. So big pharma have said, Fine, thats great; now we understand. I think that you will find a lot more interest in the cannabinoid system now that Sativex has been approved.. So what is the current state of cannabinoid research? As the head of one of the worlds leading cannabinoid research groups, Guy is well-positioned to comment. One of his fundamental tasks is to debunk the myths and preconceptions about this emerging area of science. We have to take more care to provide far more fundamental data than if wed just invented a molecule and said, Look, this is what it does, please accept it. So there is an education process. And its very cultural, very different throughout ...
Background: In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.. Methodology/Principal Findings: Phosphorylated Akt immunoreactivity (pAkt-IR) scores were available in the database. CB1 receptor immunoreactivity (CB1IR) was rescored from previously published data using the same scale as pAkt-IR. There was a highly significant correlation between CB1IR and pAkt-IR. Further, cases with high expression levels of both biomarkers were much more likely to have a more severe form of the disease at diagnosis than those with low expression levels. The two biomarkers had additive effects, rather than an ...
Cannabinoids bind the cannabinoid receptors CB1 and CB2, expressed both in the central nervous system as well as in the periphery. The affinity to the receptors varies between the cannabinoid and while some may bind CB1 or CB2, others have the affinity to bind both. Furthermore, some of the cannabinoids act as agonists to the receptor while others exert antagonistic effects. The endogenous ligands of the receptors (endocannabinoids) are lipophilic signaling molecules, similar to the phytocannabinoids.. CB receptors are G-coupled receptors leading to decreased levels of cyclic AMP and thus to an inhibitory effect. They have been shown to possess a role in various physiological and pathological processes. Thus, the endocannabinoid system participate in neurotransmission, neurogenesis, modulation of insulin metabolism, proliferation and immune system modulation. However, it has been shown that cannabinoids exert some of their effects via a non CB receptor dependent mechanism.. ...
Title:Male and Female Rats Differ in Brain Cannabinoid CB1 Receptor Density and Function and in Behavioural Traits Predisposing to Drug Addiction: Effect of Ovarian Hormones. VOLUME: 20 ISSUE: 13. Author(s):Maria Paola Castelli, Paola Fadda, Angelo Casu, Maria Sabrina Spano, Alberto Casti, Walter Fratta and Liana Fattore. Affiliation:CNR National Research Council of Italy, Neuroscience Institute - Cagliari, @ Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato (Cagliari), Italy.. Keywords:Sex difference, ovariectomy, oestrogen, CB1 receptor and [35S]GTPγS binding, locomotor activity, social interaction, anxiety, prepulse inhibition.. Abstract:Sex-dependent differences are frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. We recently demonstrated a modulating effect of sex and oestrous cycle on cannabinoid-taking and seeking ...
Contributions from chemistry to the area of life sciences are enormous. Chemicals in natural or synthetic forms have been used in health and clinical areas as long as history can be traced, and advancements in humanitys understanding of the chemical nature of making and breaking bonds have contributed to unprecedented developments in clinical chemistry. A section in this issue of The Chemist is dedicated to the theme Clinical Chemistry edited by Dr. Margot Hall. Dr. Hall was kind enough to solicit manuscripts for this themed section, as well as doing all the hard work associated with the process of editing it. For a summary of the manuscripts in this section, I encourage you to read the guest editorial by Dr. Hall in this issue of the journal. In addition to the themed section on Clinical Chemistry, there are contributions from others. Bethany Davis describes a thought provoking way to encourage the participation of girls in chemistry through exploring the chemistry of makeup. She was invited ...
A section in this issue of The Chemist is dedicated to the theme Clinical Chemistry edited by Dr. Margot Hall. Dr. Hall was kind enough to solicit manuscripts for this themed section, as well as doing all the hard work associated with the process of editing it. For a summary of the manuscripts in this section, I encourage you to read the guest editorial by Dr. Hall in this issue of the journal. In addition to the themed section on Clinical Chemistry, there are contributions from others. Bethany Davis describes a thought provoking way to encourage the participation of girls in chemistry through exploring the chemistry of makeup. She was invited to write this piece in The Chemist based upon her well-known outreach efforts to promote chemistry among girls in schools and colleges. Encouraging the participation of women in general in the sciences is a national priority. On the other topics, Leah Eller presents a review of the book Organic Structure Analysis (second edition), and Kenneth Abate ...
Tylenol/Acetaminophen is a synthetic cannabinoid Its in reality a cannabinoid prodrug. After a few metabolic steps, it reaches the talent and combines with arachidonic acid to shape AM404. Now AM404 is surely a hell of a cannabinoid, and is idea to be responsible for most, if not all of the…
Liver fibrosis, a major contributor to liver-related mortality with lack of effective treatment. It is associated with increased activity of the CB1R system, and the CB1R antagonist rimonabant mitigates fibrosis in animal models. However, the antifibrotic efficacy is low, and neuropsychiatric side effects halted its therapeutic development. Liver fibrosis is also associated with increased activity of iNOS, and iNOS inhibitors have been shown to mitigate liver fibrosis. In order to improve the safety and antifibrotic efficacy of CB1R antagonism, we have developed highly potent, orally bioavailable hybrid CB1R antagonists that are behaviorally inactive due to low brain penetrance, and have additional activity as iNOS inhibitors. We have tested the antifibrotic efficacy of the compound in a liver fibrosis induced by bile-duct ligation (BDL). (-)-MRI1867 (CB1R antagonist/iNOS inhibitor) selectively block peripheral CB1R (Ki 2.5 nM) due to its low brain penetrance. (-)-MRI1867 directly inhibits iNOS ...
The aim of this study was to determine if the neutral cannabinoid CB₁ receptor antagonist, AM4113, regulates body weight in the rat via changes in food intake. We confirmed that the AM4113-induced reduction in food intake is mediated by CB₁ recep
Cannabinoid-1 receptors (CB1R) exist primarily on central and peripheral neurons, where activation of these receptors is associated with regulation of neurotransmitter release.. Cannabinoid-2 receptors (CB2R) are found mainly on immune cells and in selected areas of the nervous system. Drugs targeting these receptors have been demonstrated to have anti-inflammatory actions.. Cannabinoid receptors, endocannabinoids and biosynthetic and degradative enzymes for these endogenous ligands form the endocannabinoid sytem. This important biological system is upregulated during sepsis, suggesting that drugs that modulate the endocannabinoid system may represent a therapeutic target in the treatment of local and systemic inflammation associated with sepsis.. However, to date, experimental studies involving CB1R and CB2R ligands in models of sepsis have been contradictory and it is unclear whether cannabinoids mediate pro- or anti- inflammatory actions, or what the contribution of individual cannabinoid ...
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ABSTRACT: Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects. However in this context, little is known about how selective activation of the cannabinoid type-2 receptor (CB2R) affects the activated state of the brain endothelium and blood brain ... Continue Reading ...
Cannabinoid/Terpene Profile. Cannabinoid profiling during the growing stage enables the identification of plants that might have unique cannabinoid profiles of interest. These plants can provide growers with differentiated products and a competitive advantage in the market. Performing an analysis of compounds like cannabidiolic acid (CBDA) while a plant is still growing provides useful information for the optimization of growing conditions. Terpene profiling is also important as terpenes are primarily responsible for the taste and smell of cannabis. A terpene profile will provide further data in developing differentiated strains or products with optimum organoleptic qualities.. ...
SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has recently been reported to reverse biochemical, physiological and behavioral effe
Cannabinoids have long been known to have potent psychotropic actions, but their wide-ranging effects on the cardiovascular system are just beginning to be unraveled.. In anesthetized rat models, intravenously administered anandamide produces a triphasic hemodynamic response (28): a brief period of vagally mediated bradycardia and hypotension, followed by a transitory pressor reaction, and a relatively prolonged vasodepressor response. The latter is the dominant effect of anandamide in animal models, and it results from CB1-mediated inhibition of norepinephrine release from presynaptic nerve terminals (29). In humans, acute administration of the cannabinoids produces vasodilation and tachycardia with a variable net effect on systemic blood pressure (30), but long-term use of THC results in CB1-mediated hypotension and bradycardia (31,32).. Although CB1receptors are mostly expressed on the neuronal terminals, there is evidence showing that other cell types express these receptors and participate ...
The cannabinoid 1 receptor (CB1R) is one of the most abundant G protein-coupled receptors (GPCRs) in the central nervous system. CB1R involvement in multiple physiological processes, especially neurotransmitter release and synaptic function, has made this GPCR a prime drug discovery target, and pharmacological CB1R activation has been demonstrated to be a tenable therapeutic modality. Accordingly, the design and profiling of novel, drug-like CB1R modulators to inform the receptors ligand-interaction landscape and molecular pharmacology constitute a prime contemporary research focus. For this purpose, we report utilization of AM3677, a designer endocannabinoid (anandamide) analogue derivatized with a reactive electrophilic isothiocyanate functionality, as a covalent, CB1R-selective chemical probe. The data demonstrate that reaction of AM3677 with a cysteine residue in transmembrane helix 6 of human CB1R (hCB1R), C6.47(355), is a key feature of AM3677s ligand-binding motif. Pharmacologically, ...
The limited effectiveness of current therapies against Alzheimers disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer. The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors, with their endogenous ligands and the enzymes related to the synthesis and degradation of these endocannabinoid compounds. ...
Definition : Immunoassay reagents intended to perform qualitative analyses on a body fluid sample (typically urine) to detect cannabinoid levels and/or cannabinoid metabolite levels in a short period of time, typically several minutes.. Entry Terms : Metabolite Determination Reagents, Cannabinoid, Rapid Test , Marijuana Rapid Test Determination Reagents , Marijuana Determination Reagents , Hashish Rapid Test Determination Reagents , Hashish Determination Reagents , Cannabinoid Determination Reagents , Cannabinoid Metabolite Reagents, Rapid Test , Cannabinoid Determination Reagents, Rapid Test , Reagents, Immunoassay, Rapid Test, Drug-of-Abuse, Cannabinoid/Metabolite. UMDC code : 20118 ...
Not too long ago, a drug called rimonabant seemed to be just such a magic bullet. Rimonabant blocked the receptors in the body that are sensitive to cannabinoids like THC. There are two known varieties of cannabinoid receptors, by the way, CB1 and CB2, though they stand among other multi-purpose receptors that are sensitive to…
α-Pinene is a monoterpene found in conifers and believed to enhance memory (Perry et al., 2000). α-Pinene did alter neurotransmission, but like limonene, it did reduced CB1 signaling (F(6,84)=3.198, P=0.0071).. Discussion. Terpenoids are cannabinoid-associated terpenes that are continuing to find their way into consumer interests due to their often-claimed therapeutic benefits, though there is little understanding of their actual effects on cannabinoid signaling. We tested several of the more widely promoted terpenes: myrcene, linalool, limonene, α-pinene, and nerolidol in a well-characterized neuronal model that utilizes endogenous cannabinoid signaling. Our chief findings are that most terpenoids either had no effect, or a modest inhibitory effect on cannabinoid signaling at 1μM. The exception was nerolidol, which had dual, opposing effects. Nerolidol reduced cannabinoid signaling, likely by inhibiting endocannabinoid synthesis, but also enhanced maximal CB1 signaling. This suggests that ...
A pentacyclic hybrid cannabinoid (4) has been synthesized, which combines structural elements of traditional cannabinoids and cannabmimetic indoles. Cannabinoid 4 contains a 1-pentylindole structure fused to the 2,3-positions of the partially reduced hydroxydibenzopyran system of THC. The successful approach to 4 employed 9-benzoyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole (17) as the starting material.
To get a free copy of An Easy Guide to Breastfeeding for African American Women, visit http://www.womenshealth.gov/pub/BF.AA.pdf.. National Breastfeeding Hotline 1-800-994-9662 (Available 9 a.m. - 6 p.m. M-F, EST). African American Breastfeeding Alliance 1-877-532-8535. International Board Certified Lactation Consultant-To find an IBCLC near you, visit http://www.ilca.org. La Leche League International 1-800-LA LECHE or 1-847-519-7730 or visit http://www.lalecheleague.org. La Leche League International has trained mothers who have breastfed their own babies known as La Leche League Leaders. These women are available to answer any and all questions about breastfeeding. The local La Leche League contact information for Memphis, TN is: LLL of Memphis East Melanie 901-324-8215. LLL of Germantown Emily 901-685-8832. Phone Help from LLL: Anne 901-251-9036 - phone help only LLL of Memphis East meets on the first Thursday of each month at 10:30 a.m. at the St. Johns Episcopal Church - Family Life ...
We are delighted to announce that the Physical Chemistry Chemical Physics (PCCP) themed collection Photodissociation and reaction dynamics is now online and free to access until 1 October 2019.. Guest-edited by Andrew Orr-Ewing (University of Bristol), this themed issue highlights the latest research in the fundamental mechanisms of photochemical and chemical reactions in the gas and liquid phases, featuring both experimental and theoretical studies. ...
The themed issue, Catalysis in Flow Chemistry, guest-edited by Steven Ley (University of Cambridge), features key contributions on the use of catalysis in flow chemistry applications. This important developing area of science encompasses homogeneous, heterogeneous and enigmatic systems, with an emphasis on using continuous flow based technologies.. Read the full themed collection here. ...
Tamoxifen-inducible genetic inactivation of cannabinoid type 1 (CB1) receptor in TPH2-positive neurons. (A) Schematic illustrations of CB1fl/fl allele before (a
Abstract The possible role of the CB2 receptor (CB2r) in psychiatric disorders has been considered. Several animal models use knockout (KO) mice that...
THCV is a cannabinoid that has garnered much attention for its ability to suppress appetite. The obscure compound is explored and explained in this post.
4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide: a CB1 cannabinoid receptor radioligand for PET imaging
Mol Med Rep 12: [Related article:] 7963-7970, 2015; DOI: 10.3892/mmr.2015.4477. Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Fig. 4B. The images captured at the 0 h time point, illustrating the addition of the synthetic cannabinoid, WIN55, 212-2 (WIN), to the BEL7402 hepatocellular carcinoma cells (at concentrations of 5 and 10 µM; upper panels, the centre image and the right image, respectively) were inadvertently selected from the same original image. An error was made during the compilation of this Figure, and an incorrect image was selected for Fig. 4B, the upper right panel (showing the addition of 10 µM WIN). A corrected version of Fig 4 is presented, showing the correct data for Fig. 4B, which pertain to the 0 h time point on addition of 10 µM WIN to the cells. This error did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the ...
Pharmaxis in Australia was actively engaged in a research programme focused on developing orally-available, synthetic selective cannabinoid receptor ligands,
A list of the journals that are reviewed and the criteria for selecting articles from these journals for inclusion in Evidence-Based Nursing are included in each issue. The following articles passed all criteria but were not abstracted because, in the judgment of the editors, their findings were less widely applicable to nursing practice, the topic was of interest to only a select group of nurse specialists, or the topic was recently addressed in another abstract. ...
A list of the journals that are reviewed and the criteria for selecting articles from these journals for inclusion in Evidence-Based Nursing are included in each issue. The following articles passed all criteria but were not abstracted because, in the judgment of the editors, their findings were less widely applicable to nursing practice, the topic was of interest to only a select group of nurse specialists, or the topic was recently addressed in another abstract. ...
The Kidney Dialysis Foundation (KDF) is a non-profit charitable organisation that provides subsidised dialysis treatment to needy members of our community.
http://gerrit.cloudera.org:8080/4535 to look at the new patch set (#2). Change subject: cache: fix behavior on single-CPU systems ...................................................................... cache: fix behavior on single-CPU systems On a system with only a single CPU, shard_bits_ would be set to 0. This would then result in calculating hash ,, (32 - 0) which is undefined behavior. With optimizations, this would turn into a no-op, and wed end up using the whole hash as the shard index, instead of 0, causing a crash. The fix is to widen the hash to uint64_t before shifting. Tested by manually making NumCPUs return 1 and running cache-test. Change-Id: I7809e5697df657a589b2ceae5c6d4edbf161b52a --- M src/kudu/util/cache.cc 1 file changed, 3 insertions(+), 1 deletion(-) git pull ssh://gerrit.cloudera.org:29418/kudu refs/changes/35/4535/2 -- To view, visit http://gerrit.cloudera.org:8080/4535 To unsubscribe, visit http://gerrit.cloudera.org:8080/settings Gerrit-MessageType: newpatchset ...
With a clean and minimalist style, this print depicts the names and chemical structures of 20 different cannabinoid molecules including THC, CBD, CBC, etc.
Bikramjeet Vig has posted comments on this change. ( http://gerrit.cloudera.org:8080/8233 ) Change subject: IMPALA-6002: Add a LLVM diagnostic handler for LLVM linker errors ...................................................................... Patch Set 3: (1 comment) http://gerrit.cloudera.org:8080/#/c/8233/1/tests/query_test/test_codegen.py File tests/query_test/test_codegen.py: http://gerrit.cloudera.org:8080/#/c/8233/1/tests/query_test/[email protected] PS1, Line 45: def test_codegen_diagnostic_handler(self, vector): , You could probably test this in be/src/codegen/llvm-codegen-test.cc with co Done -- To view, visit http://gerrit.cloudera.org:8080/8233 To unsubscribe, visit http://gerrit.cloudera.org:8080/settings Gerrit-Project: Impala-ASF Gerrit-Branch: master Gerrit-MessageType: comment Gerrit-Change-Id: I907ff1f8975c02d422b4a669afbfc2e536ddf1ff Gerrit-Change-Number: 8233 Gerrit-PatchSet: 3 Gerrit-Owner: Bikramjeet Vig ,[email protected], Gerrit-Reviewer: Bikramjeet Vig ...
We have demonstrated previously that mouse and human islets express ECS (endocannabinoid system) elements, and that short-term activation of islet cannabinoid CB1r and CB2r (cannabinoid type 1 and 2 receptors respectively) stimulates insulin secretion in vitro. There is evidence that the ECS is overactive in Type 2 diabetes, impairing glucose homoeostasis, but little is known about whether it is implicated in islet dysfunction. Therefore the aim of the present study was to investigate the effect of chronic exposure of isolated mouse islets to cannabinoid receptor agonists on islet gene expression and function. Quantitative RT-PCR (reverse transcription-PCR) indicated that mRNAs encoding synthesis [NAPE-PLD (N-acyl-phosphatidyl ethanolamide-hydrolysing phospholipase D)] and degradation [FAAH (fatty acid amide hydrolase)] of the endocannabinoid AEA (anandamide) were the most abundant ECS elements in mouse islets, with much lower levels of CB1r, CB2r, DAGL (diacylglycerol lipase) and MAGL ...
Using RNA (Northern) blot hybridization and reverse transcription-PCR, we demonstrate that the brain-type cannabinoid receptor (CB1-R) mRNA, but not the spleen-type cannabinoid receptor (CB2-R) mRNA, is expressed in the mouse uterus and that this organ has the capacity to synthesize the putative endogenous cannabinoid ligand, anandamide (arachidonylethanolamide). The psychoactive cannabinoid component of marijuana--delta 9-tetrahydrocannabinol (THC)--or anandamide, but not the inactive and nonpsychoactive cannabidiol (CBD), inhibited forskolin-stimulated cyclic AMP formation in the mouse uterus, which was prevented by pertussis toxin pretreatment. These results suggest that uterine CB1-R is coupled to inhibitory guanine nucleotide-binding protein and is biologically active. Autoradiographic studies identified ligand binding sites ([3H]anandamide) in the uterine epithelium and stromal cells, suggesting that these cells are perhaps the targets for cannabinoid action. Scatchard analysis of the ...
The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB1 and CB2), as well as monoacylglycerol lipase (MAGL), the enzyme that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data show that CB1 receptor is highly expressed from embryonic day 5 (E5) until post hatched day 7 (PE7), decreasing its levels throughout development. CB1 is densely found in the ganglion cell layer (GCL) and inner plexiform layer (IPL). CB2 receptor was also found from E5 until PE7 with a decrease in its contents from E9 afterwards. CB2 was mainly present in the lamination of the IPL at PE7. MAGL is expressed in all retinal layers, mainly in the IPL and OPL from E9 to PE7 retina. CB1 and CB2 were found both in neurons and glia cells, but MAGL was only expressed in Müller glia. Older retinas (PE7) show CB1
Previous experiments have shown that LTP of field potential recordings in the hippocampus is blocked by cannabinoid receptor activation (Nowicky et al., 1987; Collins et al., 1994, 1995; Terranova et al., 1995). This inhibition could be caused by a direct effect on the protein(s) involved in long-term synaptic plasticity. Activation of cannabinoid receptors has been found to inhibit the production of cAMP via activation of a G-protein to which the receptor is coupled (Bidaut-Russell et al., 1990; Deadwyler et al., 1995). This decrease in cAMP could, in turn, reduce the activity of cAMP-dependent protein kinase, which has been identified as an important modulator of LTP (Brandon et al., 1997). Other direct effects on proteins involved in LTP and LTD are possible. However, cannabinoid receptor-mediated G-protein activation is also known to inhibit release of neurotransmitter in cultured hippocampal neurons (Shen et al., 1996). To determine whether cannabinoid receptor activation inhibits long-term ...
In a well-publicized article in the February 23, 2005 issue of the Journal of Neuroscience, researchers from Spain describe changes in cannabinoid receptors in the brains of AD patients, as well as animal behavioral and in-vitro data suggesting that cannabinoid agonists can protect neurons by reducing microglial activation.. The headlines on this study were predictably tantalizing (see, for example, Marijuana May Block Alzheimers), but also misleading. The mass media stories barely dug beyond the papers stated implication that marijuanas active ingredients could stem the progression of neurodegeneration. In reality, however, the story is more complicated and still unfolding. To begin with, two cannabinoid receptors have been identified. CB1 is the major type in brain, expressed by all types of nervous system cells, and apparently responsible for the psychoactive effects of the drug. CB2 is mainly expressed in immune system cells, but also in microglia (Benito et al., 2003), and may mediate ...
TY - JOUR. T1 - Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration. T2 - implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. AU - Sousa, Vasco C. AU - Assaife-Lopes, Natália. AU - Ribeiro, Joaquim A. AU - Pratt, Judith A. AU - Brett, Ros R. AU - Sebastião, Ana M. PY - 2011. Y1 - 2011. N2 - The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor ...
What is the role of cannabinoid receptor type 1 (CB1) in olfactory processing? In this podcast, Editor-in-Chief Bill Yates talks with Thomas Heinbockel (Howard University) and Alex Straiker (Indiana University, Bloomington) about their recent study in mice, which revealed that CB1 is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). Listen to learn about the endocannabinoid system, mitral cells, implications for olfactory behavior, and more!. Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory ...
We have investigated the adaptive changes of the human central cannabinoid receptor (CB1) stably expressed in Chinese hamster ovary cells (CHO-CB1), after agonist (CP 55,940) or selective CB1 inverse agonist (SR 141716) treatment. CB1 receptor density and affinity constant as measured by binding assays with both tritiated ligands remained essentially unchanged after varying period exposure of CHO-CB1 cells (from 30 min to 72 hr) to saturating concentrations of CP 55,940 or SR 141716. However, using a C-myc-tagged version of the CB1 receptor, FACS analysis and confocal microscopy studies on CB1 expression indicated that the agonist promoted a disappearance of cell surface receptor although inverse agonist increased its cell surface density. Taken together these results suggest that 1) agonist induces internalization of the receptor into a cellular compartment that would be still accessible to both the hydrophobic ligands CP 55,940 or SR 141716; 2) inverse-agonist promotes externalization of the ...
The actions of THC result from its partial agonist activity at the cannabinoid receptor CB1 (Ki = 10 nM[20]), located mainly in the central nervous system, and the CB2 receptor (Ki = 24 nM[20]), mainly expressed in cells of the immune system.[21] The psychoactive effects of THC are primarily mediated by the activation of cannabinoid receptors, which result in a decrease in the concentration of the second messenger molecule cAMP through inhibition of adenylate cyclase.[22]. The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such as anandamide and 2-arachidonoyl glyceride (2-AG). THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling, as the drug has a relatively low cannabinoid receptor efficacy and affinity. In populations of low cannabinoid receptor density, THC may act to antagonize endogenous agonists that possess greater receptor efficacy.[23] THC is a ...
Looking for cannabinoid? Find out information about cannabinoid. Any one of the various chemical constituents of cannabis , that is, the isomeric tetrahydrocannabinols, cannabinol, and cannabidiol Explanation of cannabinoid
In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimers disease, Parkinsons disease and Huntingtons disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure. Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are ...
Basal Ganglia. CB1 receptors are expressed throughout the basal ganglia and have well established effects on movement in rodents. As in the hippocampus, these receptors inhibit the release of glutamate or GABA transmitter, resulting in decreased excitation or reduced inhibition based on the cell they are expressed in. Consistent with the variable expression of both excitatory glutamate and inhibitory GABA interneurons in both the basal ganglias direct and indirect motor loops, synthetic cannabinoids are known to influence this system in a dose-dependent triphasic pattern. Decreased locomotor activity is seen at both higher and lower concentrations of applied cannabinoids, while an enhancement of movement may occur upon moderate dosages. However, these dose-dependent effects have been studied predominately in rodents and the physiological basis for this triphasic pattern warrants future research in humans. Effects may vary based on the site of cannabinoid application, input from higher cortical ...
Several 3-acylindoles with high affinity for the CB(2) cannabinoid receptor and selectivity over the CB(1) receptor have been prepared. A variety of 3-acyl substituents were investigated, and the tetramethylcyclopropyl group was found to lead to high affinity CB(2) agonists (5, 16). Substitution at …
The cannabinoid signaling plays a significant role in controlling the local immune response on the skin. It has been found from research that endocannabinoids and phytocannabinoids modulated immune fluctuations. The homeostatic signaling of the ECS through its receptors CB1 and CB2 helps keep the production and release of pro-inflammatory cytokines and chemokines under control.. Cannabidiol (CBD) positively influences the endocannabinoid system (ECS) through its receptors CB1 and CB2. Due to this, it produces an anti-inflammatory effect when applied topically for cutaneous inflammation. Apart from this, other cannabinoids found in the hemp plant like cannabigerol (CBG), cannabichromene (CBC), CBGV, CBDV, And THCV are also known to produce anti-inflammatory effects when applied to the skin.. Apart from the above-mentioned skincare effects, the high lipid content of cannabidiol products like CBD oil helps to soothe the skin when applied topically. Also, the antioxidants contained in it helps with ...
Cannabinoid Complex by Boulder Botanicals: Is it legal? How effective is this full spectrum phytocannabinoid formula? How does Cannabinoid Complex work? Is this CBD supplement safe? Read this and more in our full review of Boulder Botanicals Cannabinoid Complex.
In 2018, Export of Sinkers, Needles and Other Articles Used in Forming Stitches from Pakistan was 6794 US Dollars. Discover more data with NationMaster!
Toxoplasma gondii, an obligate intracellular parasite, infects more than 30% of world's population. This parasite is considered to be neurotropic, and has high tropism for the central nervous system, and potentially induces cryptogenic epilepsy by no clear mechanism. The current study aimed to investigate the alteration of the main components ...
The cannabinoid receptors are cells spread throughout your body and there are at least two types of receptors that work as part of your endocannabinoid
It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR signaling for the Gi protein-mediated CB1R signaling was described as one of its main biochemical characteristics. However, recent studies have questioned the localization of functionally significant A2AR-CB1R heteromers in striatal glutamatergic terminals. Using a peptide-interfering approach combined with biophysical and biochemical techniques in mammalian transfected cells and computational modeling, we could establish a tetrameric quaternary structure of the A2AR-CB1R heterotetramer. This quaternary structure was different to the also tetrameric structure of heteromers of A2AR with adenosine A1
Just How Cannabinoid Receptors Unlock Relief Of Pain and much more Youve heard the narrative that is well-worn Cannabis and cannabinoids are bad for you
Approval of cannaboside pharmaceutical research included review by FDA and California Research Advisory Panel. LOS ANGELES, CA-(Marketwired - Dec 21, 2016) - Vitality Biopharma, Inc. (OTCQB: VBIO) (Vitality Biopharma, Vitality, or the Company), a corporation dedicated to the development of cannabinoid prodrug pharmaceuticals, and to unlocking the power of cannabinoids for the treatment of serious neurological and inflammatory disorders, today announced that it has received approval from both the U.S. Drug Enforcement Agency (DEA) and the State of California Research Advisory Panel which permits the Company to scale up activities at its facilities used for the development of novel cannabinoid pharmaceutical prodrugs.. Vitality has been working with the DEA to ensure adequate on-site measures are in place to prevent diversion of Schedule I controlled substances. As a component of this process, Vitalitys preclinical studies for its proprietary prodrugs of CBD and THC were reviewed and ...
The first patient has been treated in the trial of a new drug that might help people suffering from mesothelioma-related weight loss. The drug is a synthetic cannabinoid called ART27.13. A cannabinoid is a compound that acts on the CB1 and CB2 receptors of the endocannabinoid system. There are a number of cannabinoid drugs on the market. But several of them have significant side effects, including effects on the brain. Preclinical data on ART27.13 suggest that it may stimulate the appetite and counter mesothelioma-related weight loss with fewer unwanted side effects. The Cancer Appetite Recovery Study (CAReS) is a Phase I trial to test it in people. The Danger of Mesothelioma-Related Weight Loss Over 60 percent of late-stage cancer patients … Continue reading Mesothelioma-Related Weight Loss: Synthetic Cannabinoid Might Help ». ...
TY - CHAP. T1 - Cannabinoid receptors and their ligands in brain and other tissues. AU - Pertwee, Roger Guy. PY - 1999/4/5. Y1 - 1999/4/5. M3 - Chapter. SN - 089603593X. SN - 978-0896035935 SP - 177. EP - 185. BT - Marihuana and Medicine. A2 - Nahas, G.G.. A2 - Sutin, K.M.. A2 - Harvey , D.J.. A2 - Agurell, S.. PB - Humana Press. CY - Totowa, NJ, USA. ER - ...
TY - JOUR. T1 - Cannabinoid receptor 2 activation. T2 - A means to prevent monocyte-endothelium engagement. AU - Buch, Shilpa J.. PY - 2013/11. Y1 - 2013/11. UR - http://www.scopus.com/inward/record.url?scp=84886695905&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84886695905&partnerID=8YFLogxK. U2 - 10.1016/j.ajpath.2013.08.003. DO - 10.1016/j.ajpath.2013.08.003. M3 - Comment/debate. C2 - 24055258. AN - SCOPUS:84886695905. VL - 183. SP - 1375. EP - 1377. JO - American Journal of Pathology. JF - American Journal of Pathology. SN - 0002-9440. IS - 5. ER - ...
References for Abcams Cannabinoid Receptor I peptide (320-334) (ab45820). Please let us know if you have used this product in your publication
The recently cloned CB2 cannabinoid receptor subtype was stably transfected into AtT-20 and Chinese hamster ovary cells to compare the binding and signal transduction properties of this receptor with those of the CB1 receptor subtype. The binding of [3H]CP 55,940 to both CB1 and CB2 was of similar high affinity (2.6 and 3.7 nM, respectively) and saturable. In competitive binding experiments, (-)-delta 9-tetrahydrocannabinol and CP 55,940 were equipotent at the CB1 and CB2 receptors, but WIN 55212-2 and cannabinol bound with higher affinity to the CB2 than the CB1 receptor. HU 210 had a higher affinity for the CB1 receptor. Anandamide, a recently identified endogenous cannabinoid agonist, was essentially equipotent at both receptor subtypes. The structurally related fatty acid ethanolamides dihomo-gamma-linolenylethanolamide and mead ethanolamide also bound with relatively equal affinity to both receptors, but adrenylethanolamide had a higher affinity for the CB1 receptor. The rank order of ...
Cannabinoid Profile testing Licensed and accredited at both our Portland and Medford locations, EVIO Labs Oregon testing meets or exceeds requirements in the State of Oregon for cannabinoid analysis. Our Oregon locations both currently report on 17 cannabinoids, including THC, THCA, CBD and CBDA.
I came across the Phoenix Tears and i have read about the Rick Simpson Hemp oil a lot and saw that he could provide me with Hemp medication to my surprise Cannabinoid Benefits the medication was procured and delivered within 48 hours and i have been on treatment for the past 3 months. Am now here to testify that am no more a cancer patient I have experience a total transformation in my health sector with Rick Simpson Hemp oil service. Cannabinoid Benefits for all cancer patient that live in the America and Canada region get your Hemp oil from anonymously Thanks so much to Rick Simpson for providing us with his Cannabis Oil medication that has been successfully used in curing my wife breast cancer which she has been suffering from for past 6years.. We also appreciate your approachability and willingness to speak with my wife before and after she has been cured. hash oil cartridges for e cig Thank you again for helping to create the next generation of medication. We hope to assist you in the ...
I came across the Phoenix Tears and i have read about the Rick Simpson Hemp oil a lot and saw that he could provide me with Hemp medication to my surprise Cannabinoid Benefits the medication was procured and delivered within 48 hours and i have been on treatment for the past 3 months. Am now here to testify that am no more a cancer patient I have experience a total transformation in my health sector with Rick Simpson Hemp oil service. Cannabinoid Benefits for all cancer patient that live in the America and Canada region get your Hemp oil from anonymously Thanks so much to Rick Simpson for providing us with his Cannabis Oil medication that has been successfully used in curing my wife breast cancer which she has been suffering from for past 6years.. We also appreciate your approachability and willingness to speak with my wife before and after she has been cured. hash oil cartridges for e cig Thank you again for helping to create the next generation of medication. We hope to assist you in the ...
Cannabinoids and Opioids. There appears to be a synergistic analgesic (pain-relieving) benefit when cannabinoids are added to opioid treatment for pain in which there is a greater-than-additive benefical effect with the addition of cannabinoids. Studies indicate a trend towards reduced use of opioids when patients taking opioids add cannabinoids to their regimen. It is not uncommon for patients started on cannabinoids to be able to taper down or off opioids.. Interestingly, animal studies suggest that cannabinoids may reduce the development of tolerance to the analgesic benefits of opioids, resulting in less need for opioid dose escalation.. There is no enhancement of cardiorespiratory suppression from opioids with the addition of cannabinoids due to the very low density of cannabinoid (CB) receptors in brainstem cardiorespiratory centers. There does not appear to be any significant interactions with opioids regarding a cannabinoid effect on the metabolism of most opioids. However, there is ...
33. The method of claim 32, wherein the CB-2 receptor inverse agonist comprises a compound of ##STR00190## wherein D and D are independently --H, --OH, --ORa, (C1-C6)alkyl or ##STR00191## Ra, Ra, and Ra are independently selected from the group consisting of H, straight or branched chain (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C14)aryl, (C3-C14)hetero cyclo alkyl-(C1-C6)alkylene-, (C3-C14)hetero aryl-(C1-C6)alkylene-, or (C3-C14)aryl(C1-C6)alkylene-; A, B and Q are each independently (C1-C6)alkylene, (C2-C6)alkenylene or (C2-C6)alkynylene, e, f and g independently are integers between 0 and 6 inclusive; V, W, X, Y, and Z are each independently a bond, --C(R)2--, --CR--, --NR--, --N--, --O--, --C(O)--, or --S--, wherein no two adjacent members of V, W, X, Y, and Z are simultaneously --O--, --S--, or --NR--; R is H, --OH, --ORa, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, --NH2, --NH(C1-C6)alkyl, --N[(C1-C6)alkyl]2, ...
Rimonabant is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States. This decision was made after a U.S. advisory panel recommended the medicine not be approved because it may increase suicidal thinking and depression.
AequoScreen® Double Transfected Cell Lines: Cannabinoid, CB1 subtype. Human Recombinant, in CHO-K1 host cell. Two vials of cryopreserved cells are shipped per order. A detailed technical dossier includes sequence, culture conditions and pharmacological properties of the recombinant receptor. All cell lines are tested for the absence of mycoplasma. Terms and conditions apply. Some products are not available in some countries. Please inquire at your local sales office for more information.. Features:. ...
A new study from the University of Texas M. D. Anderson Cancer Centre has shown that the cannabinoid cell surface receptor CB1 plays a key role in suppressing tumour growth in colorectal
Monkey-Toes is a playful line of fun animal and insect themed footwear for children. Our original collection of hand-painted sneakers and matching socks is designed with both parents and kids in mind.Monkey-Toes make the everyday activity of putting on shoes and socks more fun by introducing friends for the feet, all while providing quality footwear for children.The Monkey-Toes family consists of five original designs - Buzzy Bees (bumblebee themed), Little Ladies (ladybug themed), Spunky Spiders (spider themed), Leap Frogs (frog themed), and Little Piggies (pig themed ...
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In addition to, CB1-D2 receptor heteromers, not long ago Together with the aid of biochemical and biophysical research CB1-CB2 receptor heteromers is documented in nucleus accumbens and globus pallidus [175]. Typical attribute aspect observed with CB1-CB2 receptor heteromers is, CB1 receptor antagonists blocks the result of CB2 receptor agonists and, conversely, CB2 receptor antagonists blocks the result of CB1 receptor agonists As a result demonstrating a bidirectional phenomenon of cross-antagonism [175]. These heteromers may well describe preceding conflicting effects and could serve as therapeutic targets. Modern evidence implies that dopamine modulates the activity of SNpc neurons not just by regular dopamine receptors, but additionally by CB1 receptors, probably by using N-arachidonoyl-dopamine [176]. Besides localization of CB1, the presence and functional purpose of TRPV1 on dopaminergic nigral neurons and their position in modulating synaptic transmission throughout the SNpc have also ...
AM-905 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is conformationally restricted by virtue of the double bond on its side chain, leading an increased affinity for and selectivity between CB1 and CB2 receptors.[1] It is a potent and reasonably selective agonist for the CB1 cannabinoid receptor, with a Ki of 1.2 nM at CB1 and 5.3 nM at CB2.[2] ...
This unit describes the use of cannabinoid radioligands in competitive binding assays for determining affinity parameters (IC50, Ki) of unlabeled compounds at transfected CB1 and CB2 receptors expressed in cell lines
This unit describes the use of cannabinoid radioligands in competitive binding assays for determining affinity parameters (IC50, Ki) of unlabeled compounds at transfected CB1 and CB2 receptors expressed in cell lines
PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the December 2017 issue here.. ...
Host: Core A (Dr. Sean Xie group), CVS Conference Room, School of Pharmacy, UPitt. Research Progress Update/Demonstration: Yan Zhang (master student) gave a talk titled as Modeling Simulation on Cannabinoid Receptor CB2 Signaling Pathway via Desensitization and Resensitization Yan Zhang integrated several models, including the previously reported cubic ternary complex (CTC) model with new component updated for the CB2 desensitization and resensitization kinetics.. Dr. Zhiwei Feng (Research Associate) gave a talk titled as Computer Modeling of 3D Structures of Cannabinoid Receptor Subtype CB2 activated through G-protein Coupling Process Dr. Feng presented the work on the influence of agonist and inverse agonist on the inactive and active state of CB2 from conformation to drug discovery. Dr. Feng also talked about the γ-secretase project for identifying the binding pocket with the DruGui program developed by Dr. Bahars group. γ-secretase is a potential target for Alzheimers ...
Tritium labelled SR 141716A; Tritium labeled SR 141716A; 3H SR 141716A; H-3 SR 141716A; Tritium labelled Rimonabant; Tritium labeled Rimonabant; 3H Rimonabant; H-3 Rimonabant;Tritium labelled 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; Tritium labeled 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; H-3 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; 3H 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5HT1AR binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15?18% in 5HT1AR in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5HT1AR (with increases of 44, 29, and ...
Hemopressin is a recently discovered endocannabinoid that acts as a CB1 inverse agonist (roughly meaning that it has the opposite action of THC at CB1 receptors). Most cannabinoid receptor ligands are lipids. However, Hemopressin is the founding member of a new class of endocannabindoids: the peptide cannabinoids or PepCanns. As Hemopressin actually has a higher affinity for CB1 than any other true cannabinoid, this justifies Hemopressin being classified as an endocannabinoid. Hemopressin strongly suppresses pain sensation and eating and may counteract de-myelination in diseases like Multiple Sclerosis and therefore has considerable therapeutic potential.. ...
ISSUE-135 (link-canvas-spec): put back direct link to the W3C version of the canvas 2d context spec Per the decision policy, at this time the Chairs would like to solicit volunteers to write Change Proposals for ISSUE-135: http://www.w3.org/html/wg/tracker/issues/135 http://dev.w3.org/html5/decision-policy/decision-policy.html#escalation If no Change Proposals are written by January 19, 2011 this issue will be closed without prejudice. Issue status link: http://dev.w3.org/html5/status/issue-status.html#ISSUE-135 /paulc On behalf of the HTML WG Chairs Paul Cotton, Microsoft Canada 17 Eleanor Drive, Ottawa, Ontario K2E 6A3 Tel: (425) 705-9596 Fax: (425) 936-7329 ...
... exhibits cannabinoid CB1 receptor antagonistic activity. There is considerable confusion about the absolute ... "Discovery of indole alkaloids with cannabinoid CB1 receptor antagonistic activity". Bioorganic & Medicinal Chemistry Letters. ...
... is a drug which acts as a potent and selective negative allosteric modulator of the cannabinoid CB1 receptor. Studies ... "Allosteric modulation of the cannabinoid CB1 receptor". Molecular Pharmacology. 68 (5): 1484-95. doi:10.1124/mol.105.016162. ... However while Org 27569 increases the ability of CB1 agonists to bind to the receptor, it decreases their efficacy at ... and so in practice behaves as an insurmountable antagonist of CB1 receptor function. GAT100 PSNCBAM-1 ZCZ-011 Price MR, Baillie ...
It is a tricyclic aryl derivative that acts as a competitive antagonist at the CB2 cannabinoid receptor. Its activity at CB1 ... WIN 55,212-2 WIN 55,225 Howlett AC, Berglund B, Melvin LS (October 1995). "Cannabinoid Receptor Agonists and Antagonists". ...
Cannabinoid receptor antagonist Lange JH, Kruse CG (2008). "Cannabinoid CB1 receptor antagonists in therapeutic and structural ... Reggio, Patricia H. (2009). "Toward the design of cannabinoid CB1 receptor inverse agonists and neutral antagonists". Drug ... Drinabant (INN; AVE-1625) is a drug that acts as a selective CB1 receptor antagonist, which was under investigation varyingly ... Lee HK, Choi EB, Pak CS (2009). "The current status and future perspectives of studies of cannabinoid receptor 1 antagonists as ...
There are at least two types of cannabinoid receptors (CB1 and CB2). Most cannabinoids are lipophilic (fat soluble) compounds ... Pertwee RG (January 1997). "Pharmacology of cannabinoid CB1 and CB2 receptors". Pharmacology & Therapeutics. 74 (2): 129-80. ... Cannabinoids produce a "marked depression of motor activity" via activation of neuronal cannabinoid receptors belonging to the ... The binding of cannabinoids to cannabinoid receptors decrease adenylyl cyclase activity, inhibit calcium N channels, and ...
... is a negative allosteric modulator of the cannabinoid CB1 receptor. Org 27569 PSNCBAM-1 ZCZ-011 Kulkarni PM, Kulkarni AR ... June 2016). "Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant and Signaling Profile of GAT100 ... January 2016). "Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s ...
July 2003). "Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor". The ... August 2002). "Design, synthesis and biological activity of rigid cannabinoid CB1 receptor antagonists". Chemical & ... and more selective for the CB1 receptor over CB2, than the more commonly used ligand rimonabant, with a Ki at CB1 of 350fM (i.e ... a drug used in scientific research which acts as an extremely potent and selective antagonist of the cannabinoid receptor CB1. ...
323-. ISBN 978-981-4287-59-3. Bambico, Francis Rodriguez; Gobbi, Gabriella (2008). "The cannabinoid CB1 receptor and the ... Cannabinoid receptor Synthetic cannabinoid Cannabinoid receptor antagonist George I. Papakostas; Maurizio Fava (2010). ...
"Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor". British Journal of Pharmacology. 172 (20): ... "The pharmacology of cannabinoid receptors and their ligands: an overview". International Journal of Obesity. 30 (S1): S13-S18. ... Cannabis and cannabinoids : pharmacology, toxicology, and therapeutic potential. Grotenhermen, Franjo., Russo, Ethan. New York ... OCLC 606854125.CS1 maint: others (link) Huestis, M. A. (2005), "Pharmacokinetics and Metabolism of the Plant Cannabinoids, Δ9- ...
January 1999). "Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity ... an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from ... "Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain ... 2-AG was a known chemical compound but its occurrence in mammals and its affinity for the cannabinoid receptors were first ...
It is an agonist of CB1 and CB2 Cannabinoid receptors with about half the potency of ∆9-THC in most but not all measures of ... 8-THC has been reported to have a Ki value of 44 ± 12 nM at the CB1 receptor and 44 ± 17 nM at the CB2 receptor. These values ... Pertwee, R G (2008). "The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, ... "Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation". Molecules. 25 (2): 417. doi:10.3390/ ...
AM-251 is an inverse agonist at the CB1 cannabinoid receptor. AM-251 is structurally very close to rimonabant; both are ... Discovery and development of Cannabinoid Receptor 1 Antagonists Lan R, Liu Q, Fan P, Lin S, Fernando SR, McCallion D, et al. ( ... The resulting compound exhibits slightly better binding affinity for the CB1 receptor (with a Ki value of 7.5 nM) than ... February 1999). "Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists". Journal of ...
It is used in scientific research for mapping the distribution of CB1 receptors. AM-694 is an agonist for cannabinoid receptors ... a CB1 cannabinoid receptor ligand". Journal of Labelled Compounds and Radiopharmaceuticals. 46 (9): 799-804. doi:10.1002/jlcr. ... is a designer drug that acts as a potent and selective agonist for the cannabinoid receptor CB1. ... AM-679 AM-1235 AM-2201 AM-2232 AM-2233 FUBIMINA JWH-018 List of AM cannabinoids List of JWH cannabinoids THJ-2201 Willis PG, ...
Anandamide activates the cannabinoid receptors CB1 and CB2. FAAH knockout mice show increased anandamide levels in vivo and ... an orthologue of vertebrate cannabinoid receptors in the urochordate Ciona intestinalis". Gene. 302 (1-2): 95-101. doi:10.1016/ ... cannabinoid-receptor dependent behaviors including antinociception and anxiolysis. GPR18, GPR55, GPR92 have also been proposed ... An example of this is the lipid signaling system involving transient receptor potential channels (TRP), which interact with N- ...
December 2015). "A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No ... ZCZ-011 is a positive allosteric modulator of the cannabinoid CB1 receptor. GAT100 Org 27569 PSNCBAM-1 Poklis JL, Clay DJ, ... June 2015). "HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in ...
March 2011). "Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists". Bioorganic & ... heterocycle derivatives as agonists of the cannabinoid CB1 receptor.", issued 20 April 2010, assigned to Organon NV US 7763732 ... PTI-1 (SGT-48) is an indole-based synthetic cannabinoid. It is one of few synthetic cannabinoids containing a thiazole group ...
... cannabinoid CB1 / dopamine D2 heteromers, and even CB1/A2A/D2 heterotrimers where three different receptors have come together ... "Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and ... A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids". ... "Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology". Brain Research Reviews. 58 (2): 415 ...
It acts as a potent and selective cannabinoid receptor agonist, with high potency at both the CB1 and CB2 receptors, but low ... March 2011). "Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists". Bioorganic & ... April 2012). "Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain". Bioorganic & Medicinal ... heterocyclic derivatives as agonists of the CB1 receptor. Discovery of a clinical candidate". Bioorganic & Medicinal Chemistry ...
... and Raphael Mechoulam found the endogenous agonist of the cannabinoid receptor type 1 (CB1) in 2000. The discovery was 100 gram ... 3 μM at the Cannabinoid receptor type 1 and the peripheral cannabinoid receptors. The presence of 2-AGE in body tissue is ... 2-AGE binds with a Ki of 21 nM to the CB1 receptor and 480 nM to the CB2 receptor. It shows agonistic behaviour on both ... an endogenous agonist of the cannabinoid CB1 receptor". Proceedings of the National Academy of Sciences. 98 (7): 3662-3665. doi ...
... is a negative allosteric modulator of the cannabinoid CB1 receptor. GAT100 Org 27569 ZCZ-011 German N, Decker AM, ... a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats". British Journal of Pharmacology. ... "Diarylureas as Allosteric Modulators of the Cannabinoid CB1 Receptor: Structure-Activity Relationship Studies on 1-(4- ...
Mice lacking the mu opioid receptor exhibited a lack of conditioned place preference. Knockouts of CB1 cannabinoid receptor ... Castane, A., Valjent, E., Ledent, C., Parmentier, M., Maldonado, R., & Valverde, O. (2002).Lack of CB1 cannabinoid receptors ... Ethanol self-administration and ethanol conditioned place preference are reduced in mice lacking cannabinoid CB1 receptors. ... Studies also show a lack of conditioned place preference in CB1 receptor knockout mice, implicating a possible contribution of ...
... of cannabinoid CB1 receptors. It is shown that pepcan-12 opposite acts as a potent CB2 cannabinoid receptor positive allosteric ... which was originally proposed to act as a selective agonist for the CB1 cannabinoid receptor. It is a 12-amino acid polypeptide ... "Hemopressin is an inverse agonist of CB1 cannabinoid receptors". Proceedings of the National Academy of Sciences of the United ... Recently it was shown that RVD-Hpα (also called Pepcan-12) is a potent negative allosteric modulator at CB1 receptors, together ...
January 1998). "LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of ... LY-320,135 is a drug used in scientific research which acts as a selective antagonist of the cannabinoid receptor CB1. It was ... Pertwee RG (February 2005). "Inverse agonism and neutral antagonism at cannabinoid CB1 receptors". Life Sciences. 76 (12): 1307 ... and at higher doses it also binds to a range of non-cannabinoid receptors. However LY-320,135 is still fairly widely used in ...
"Novel cannabinol probes for CB1 and CB2 cannabinoid receptors". Journal of Medicinal Chemistry. 43 (20): 3778-85. doi:10.1021/ ... CBN acts as a partial agonist at the CB1 receptors, but has a higher affinity to CB2 receptors; however, it has lower ... Both THC and CBN activate the CB1 and CB2 receptors.[citation needed] CBN is not listed in the schedules set out by the United ... Cannabinol (CBN) is a mildly psychoactive cannabinoid found only in trace amounts in Cannabis, and is mostly found in aged ...
It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors. Longer forms of hemopressin containing 2-3 ... May 2010). "The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice". J. Neurosci ... December 2007). "Hemopressin is an inverse agonist of CB1 cannabinoid receptors". Proc. Natl. Acad. Sci. U.S.A. 104 (51): 20588 ... is also an agonist at CB1 cannabinoid receptors. Hemopressin is not an endogenous peptide but rather an extraction artefact [ ...
It is a potent CB1 full agonist with a Ki of 1.16 nM. Griffin G, Wray EJ, Martin BR, Abood ME (1999). "Cannabinoid agonists and ... antagonists discriminated by receptor binding in rat cerebellum". British Journal of Pharmacology. 128 (3): 684-688. doi: ... O-1125 (3-(1,1-dimethylhexyl-6-dimethylcarboxamide)-Δ8-tetrahydrocannabinol) is a research chemical which is a cannabinoid ...
"Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity". The Journal of Clinical ... AM-6545 is a drug which acts as a peripherally selective silent antagonist for the CB1 receptor, and was developed for the ... mediation and differential blockade by cannabinergics of the discriminative stimulus effects of the cannabinoid CB1 receptor ... CB-13 - a peripherally selective cannabinoid agonist O-2050 - a centrally active CB1 silent antagonist Methylnaltrexone - a ...
Gessa GL, Serra S, Vacca G, Carai MA, Colombo G (2005). "Suppressing effect of the cannabinoid CB1 receptor antagonist, ... Doggrell SA (March 2005). "Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?". Expert ... Lallemand F, De Witte P (July 2006). "SR147778, a CB1 cannabinoid receptor antagonist, suppresses ethanol preference in ... a new potent and selective antagonist of the CB1 cannabinoid receptor: biochemical and pharmacological characterization". The ...
It is found that the anti-inflammatory lipid lipoxin A4 is an endogenous allosteric enhancer of the CB1 cannabinoid receptor. ... "Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor". Proceedings of the National ... In addition to this, lipoxin A4 display a CB1 receptor-dependent protective effect against β-amyloid-induced spatial memory ... FPR2, which is now termed the ALX, ALX/FPR, or ALX/FPR2 receptor, is a G protein coupled receptor initially identified as a ...
The cannabinoid type 1 receptors (CB1) and their endogenous ligands, the endocannabinoids, present in peripheral organs, such ... and the CB1 receptor binding remain similarly reduced after 2-4 weeks of abstinence, suggests an involvement of CB1 receptors ... It had similar effects as a cannabinoid CB1 receptor antagonist, which could be reversed by co-treatment with a FAAH inhibitor ... AEA, an endogenous ligand of CB1 cannabinoid receptors, enhances food intake and energy storage, whereas OEA binds to ...
The anti-obesity drugs rimonabant and taranabant are inverse agonists at the cannabinoid CB1 receptor and though they produced ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... toll-like receptors (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors ... receptors, G protein-linked (metabotropic) hormone receptors, and enzyme-linked hormone receptors.[1] Intracellular receptors ...
transmembrane signaling receptor activity. • Wnt-activated receptor activity. • G-protein coupled receptor activity. ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... "Frizzled Receptors: FZD5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
"The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9- ... as the drug has a relatively low cannabinoid receptor efficacy and affinity. In populations of low cannabinoid receptor density ... The actions of THC result from its partial agonist activity at the cannabinoid receptor CB1 (Ki = 10 nM[20]), located mainly in ... The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such ...
taste receptor activity. • fatty acid binding. • lipid binding. • G-protein coupled receptor activity. ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... G-protein coupled receptor 120 is a protein that in humans is encoded by the GPR120 gene.[5][6] ...
... and as cholesterol-dependent modulation of CB1 cannabinoid receptors in nerve cells. The catalytic efficiency (i.e., the ratio ... dependent modulation of type 1 cannabinoid receptors in nerve cells". Journal of Neuroscience Research. 81 (2): 275-283. doi: ... "Regulation by cannabinoid receptors of anandamide transport across the blood-brain barrier and through other endothelial cells" ... whereas AMT activity instead is reduced by activation of the CB2 cannabinoid receptor, which inhibits NOS and NO release, also ...
G-protein coupled receptor signaling pathway. • signal transduction. • G-protein coupled purinergic nucleotide receptor ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... G-protein coupled purinergic nucleotide receptor activity. • G-protein coupled receptor activity. • signal transducer activity ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ...
... but other drugs such as CB1 receptor antagonists exist in this class too.[25][26] Drugs used to treat sleep disorders such as ... as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors,[67] however the implications for humans ... Kamiya T, Saitoh O, Yoshioka K, Nakata H (June 2003). "Oligomerization of adenosine A2A and dopamine D2 receptors in living ... Adrenergic stimulants, such as ephedrine, may act by directly binding and activating the receptors that norepinephrine and ...
"Cannabinoid Receptors Couple to NMDA Receptors to Reduce the Production of NO and the Mobilization of Zinc Induced by Glutamate ... through activation of the CB1 receptor.[9] As well as preventing methamphetamine (Meth) induced neurotoxicity via inhibition of ... The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in ... The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. ...
"Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... prostaglandin receptor activity. • signal transducer activity. • prostaglandin E receptor activity. • protein binding. ... Prostaglandin E2 receptor 4 (EP4). അവലംബം[തിരുത്തുക]. *↑ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000050628 - Ensembl, May ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... Galanin receptor 1 (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene.[5] ... "Galanin Receptors: GAL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it. *v ...
... opioids and cannabinoids and their action receptors inside the brain, DA, muscarinic and MOR and CB1 receptors respectively.[11 ... Similarly, the appetite suppressant rimonabant (a cannabinoid receptor antagonist) had to be withdrawn when it was linked with ... such as the leptin receptor and the MC-4 receptor) or are still awaiting characterization - Prader-Willi syndrome - in addition ... Opioid receptor-related processes in the nucleus accumbens and ventral pallidum affect the palatability of foods.[10] ...
John W. Huffman, et al. STRUCTURE-ACTIVITY RELATIONSHIPS AT THE CB1 AND CB2 RECEPTORS FOR 1-ALKYL-3-(1-NAPHTHOYL-4 AND 8- ... Cited in: The cannabinoid receptors, Reggio PH (Ed), Humana Press. .mw-parser-output cite.citation{font-style:inherit}.mw- ... which acts as a cannabinoid agonist at both the CB1 and CB2 receptors. It has mild selectivity for CB1 with a Ki of 2.3nM and ... This cannabinoid related article is a stub. You can help Wikipedia by expanding it.. *v ...
MePPEP Binds Reversibly and with High Specific Signal to Cannabinoid CB1 Receptors in Nonhuman Primate Brain". ...
Cannabinoid receptor 1 (CB1) is colocalized on orexinergic projection neurons in the lateral hypothalamus and many output ... where the CB1 and orexin receptor 1 (OX1) receptors form the CB1-OX1 receptor heterodimer.[4][9][10] ... where the CB1 and orexin receptor 1 (OX1) receptors physically and functionally join together to form the CB1-OX1 receptor ... CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. ... In conclusion, orexin receptors ...
Taste receptor 2 member 38 is a protein that in humans is encoded by the TAS2R38 gene. TAS2R38 is a bitter taste receptor; ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... G-protein coupled receptor activity. • signal transducer activity. • bitter taste receptor activity. ... TAS2R38, PTC, T2R38, T2R61, taste 2 receptor member 38, THIOT. External IDs. OMIM: 607751 MGI: 2681306 HomoloGene: 47976 ...
"Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers". ... The CB-1 receptor antagonist rimonabant has shown efficacy in reducing the effects of cannabis in users, but with a risk for ... The mechanisms that create this tolerance to THC are thought to involve changes in cannabinoid receptor function.[13] ... 2017). The health effects of cannabis and cannabinoids : the current state of evidence and recommendations for research. The ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... leukotriene receptor activity. • cysteinyl leukotriene receptor activity. • galanin receptor activity. Cellular component. • ... "Leukotriene Receptors: CysLT2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes# ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... The bombesin receptors are a group of G-protein coupled receptors which bind bombesin.. Three bombesin receptors are currently ... BB1, previously known as Neuromedin B receptor NMBR. BB2, previously known as Gastrin-releasing peptide receptor GRPR. BB3, ... previously known as Bombesin-like receptor 3 BRS3. External links[edit]. *. "Bombesin Receptors". IUPHAR Database of Receptors ...
Through testing in mouse models, it has been shown that activation of the CB-1 receptor helps reduce reactions associated with ... Treatments focusing on biological components such as cannabinoid receptors are being tested for effectiveness. ... Thus, a new target for potential treatments is activation of the CB-1 receptor. Modern research and techniques are attempting ... Reduction of Bone Cancer Pain by Activation of Spinal Cannabinoid Receptor 1 and Its Expression in the Superficial Dorsal Horn ...
Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. Bioorganic & Medicinal ... It acts as a potent and selective cannabinoid receptor agonist, with high potency at both the CB1 and CB2 receptors, but low ... Design, synthesis and structure-activity relationships of (indo-3-yl) heterocyclic derivatives as agonists of the CB1 receptor ... Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain. Bioorganic & Medicinal Chemistry Letters. 2012 ...
adenylate cyclase-activating G-protein coupled receptor signaling pathway. • G-protein coupled receptor signaling pathway. • ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... G-protein coupled receptor activity. Cellular component. • plasma membrane. • membrane. • integral component of membrane. • ...
mineralocorticoid receptor activity. • steroid binding. • G-protein coupled receptor activity. • steroid hormone receptor ... Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... Receptor/signaling modulators. Estrogens and antiestrogens. Androgen receptor modulators. Progesterone receptor modulators. ... G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... "Tachykinin Receptors: NK3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... tachykinin receptor activity. • G-protein coupled receptor activity. • signal transducer activity. • protein binding. ... "Entrez Gene: TACR3 tachykinin receptor 3".. *^ Quartara L, Altamura M (Aug 2006). "Tachykinin receptors antagonists: from ...
361] ^ Cannabinoid Receptor (CB1) Agonist Treatment in Severe Chronic Anorexia Nervosa...25 september 2008 [1] ...
Ang THC ng marijuana ay umaasal sa dalawang uri ng mga cannabinoid receptor sa tao na CB1 receptor at CB2 receptor na parehong ... 2003). "CB1 cannabinoid receptors and on-demand defense against excitotoxicity". Science 302 (5642): 84-8. Bibcode 2003Sci... ... Ang CB1 receptor ay matatagpuan sa utak at sa ilang mga peripheral tissue at ang CB2 receptor ay matatagpuan sa mga peripheral ... Ang mga cannabinoid receptor ay pinapagana ng mga cannabinoid na maaaring nalilikha mula sa loob ng katawan ng tao ( ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... There is no 5-HT1C receptor, as it was reclassified as the 5-HT2C receptor.[2] For more information, please see the respective ... The 5-HT1 receptors are a subfamily of the 5-HT serotonin receptors that bind to the endogenous neurotransmitter serotonin ( ... 5-HT7 receptor. References[edit]. *^ Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey ...
... af cannabinoid CB1-receptorer. Det er vist, at pepcan-12 modsat virker som en potent CB2 cannabinoid-receptor positiv ... a b Allosteriske modulatorer af CB1 cannabinoid receptoren: en strukturel opdaterings gennemgang. Paula Morales, et al, ... Allosteriske modulatorer af cannabinoid CB1-receptorer har potentialet til at behandle CNS og perifere forstyrrelser, samtidig ... Cannabinoid CB1-receptoren er involveret i de anxiolytiske, beroligende og amnesiske virkninger af benzodiazepiner. García- ...
Cannabinoid (CB1. *CB2, GPR (18. *55. *119)). *EBI2. *Estrogen. *Free fatty acid (1 ... Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as ... All of the prostanoid receptors are G protein-coupled receptors belonging to the Subfamily A14 of the rhodopsin-like receptor ... There are 9 established prostanoid receptors. The following table gives these receptors: a) full name; b) shortened names; c) ...
Cannabinoid receptor modulators. Receptor. (ligands). CB1. *Agonists (abridged; see here for more): 2-AG ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ... CB1 receptor antagonists. *Glycine receptor agonists. *Ketones. *Neurosteroids. *Pregnane X receptor agonists ... Nuclear receptor activity[edit]. Pregnenolone has been found to act as an agonist of the pregnane X receptor.[13] ...
long-term genetic ablation of CB1 receptors.. A number of studies have shown that CB1 receptors are expressed in the developing ... Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. A. Bilkei-Gorzo, I. Racz, O. Valverde, M. ... Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. A. Bilkei-Gorzo, I. Racz, O. Valverde, M. ... Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. A. Bilkei-Gorzo, I. Racz, O. Valverde, M. ...
Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor.. Bertini S1, Chicca A2, Gado F1, Arena C1, ... Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor ... Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor ... Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor ...
Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Zoltán Járai, Jens ... Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors ... Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors ... Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors ...
Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice.. Jin K1, Xie L, Kim SH, Parmentier-Batteur S, Sun Y, ... indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor ... Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To ... Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis. ...
Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. ... Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. ... Cannabinoid-1 receptor (CB1R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and ...
Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. ... Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. ...
CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis ... combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 ( ... CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis ... Lange, M., Daldrup, T., Remmers, F. et al. Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine ...
... Cipriano, Mariateresa Umeå ... Background: In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One ... CB1 receptor immunoreactivity (CB1IR) was rescored from previously published data using the same scale as pAkt-IR. There was a ... In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well- ...
Cannabinoid Receptor Agonists. Cannabinoid Receptor Modulators. Neurotransmitter Agents. Molecular Mechanisms of ... Cannabinoid Receptor (CB1) Agonist Treatment in Severe Chronic Anorexia Nervosa. The safety and scientific validity of this ...
... a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has recently been reported to reverse ... Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of pigeons and rats. ... SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has ... Involvement of the spinal cannabinoid receptor in nociception. Abstracts, 1995 Symposium on Cannabis and the Cannabinoids, p 44 ...
In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of ... Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and ... Dual effect of cannabinoid CB1 receptor stimulation on a vanilloid VR1 receptor-mediated response Cell Mol Life Sci. 2003 Mar; ... Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and ...
Because it is known that CB1 cannabinoid receptors are coupled to pertussis toxin-sensitive G proteins, we proposed that CB1 ... CB1 Cannabinoid Receptor-Mediated Cell Migration Message Subject (Your Name) has forwarded a page to you from Journal of ... CB1 Cannabinoid Receptor-Mediated Cell Migration. Zhao-Hui Song and Miao Zhong ... CB1 Cannabinoid Receptor-Mediated Cell Migration. Zhao-Hui Song and Miao Zhong ...
Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 ... The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 ... We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors ... We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors ...
CB1 and CB2) and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and ... These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These ... Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of ... CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. ...
CB1 receptor was determined in the adult monkey using a polyclonal antiserum raised against the amino terminus of the rat CB1 ... receptor. At the level of light microscopy, our results generally parallel earlier studie … ... The immunohistochemical distribution and subcellular localization of the cannabinoid ... A light and electron microscopic study of the CB1 cannabinoid receptor in primate brain Neuroscience. 1999;92(4):1177-91. doi: ...
The brain CB1 cannabinoid receptor is a member of the G-protein-coupled receptor superfamily (Matsuda et al., 1990; Gérard et ... The CB1 Cannabinoid Receptor Can Sequester G-Proteins, Making Them Unavailable to Couple to Other Receptors. Clemente Vásquez ... Sequestration of G-proteins by CB1 cannabinoid receptors likely occurs in two receptor states, an inactive R-GGDP state and an ... Our study suggests that CB1 cannabinoid receptors may act as dominant receptors controlling the biological signals of other ...
The mutant CB1-D164N receptor failed to sequester G-proteins.. Unlike the wild-type CB1 receptor, the mutant CB1-D164N receptor ... greater for the CB1-417 cannabinoid receptor compared with the wild-type CB1 receptor. At the 100 ng/μl injection concentration ... greater for the C-terminal-truncated CB1-417 cannabinoid receptor compared with the wild-type CB1 receptor. However, when the ... but not in CB1-417 receptors. Thus deletion of the distal C terminal of the CB1 receptor enhanced the ability of the receptor ...
... it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors ... it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors ... Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 ... Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 ...
Several evidences suggest that an alteration of cannabinoid CB1 receptor function could be involved in the pathophysiology of ... Several evidences suggest that an alteration of cannabinoid CB1 receptor function could be involved in the pathophysiology of ... Behavioral phenotypes of mice lacking cannabinoid CB1 receptors in different neuronal subpopulations. focus on sex-related ... Behavioral phenotypes of mice lacking cannabinoid CB1 receptors in different neuronal subpopulations. focus on sex-related ...
The pharmacological actions of THC result from its activity at the cannabinoid CB1 receptor, located mainly in the central ... After the discovery of endogenous ligands of CB1 and CB2 receptors and of nonclassical cannabinoids a multitude of structure- ... A Theoretical Study of the Relationships between Electronic Structure and CB1 and CB2 Cannabinoid Receptor Binding Affinity in ... hCB2 Receptor Binding Results. Table 7 indicates that the order of importance of the variables is , , . Table 8 shows that no ...
Comparison of Cannabinoid CB1 Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [18F]MK ... Mathieu Verdurand, Vu Nguyen, Daniela Stark, et al., "Comparison of Cannabinoid CB1 Receptor Binding in Adolescent and Adult ...
The CB1 cannabinoid receptor is one of the most abundant receptors in the brain and it helps to regulate movement, as well as ... Scientists find a new pharmacological target to modulate the effect of cannabinoids through their CB1 receptors 05.07.2012 ... the CB2 receptors may be a new pharmacological target for the modulation of the effect of cannabinoids through the CB1 receptor ... the CB2 receptors act as a brake on the CB1 receptors.. The research shows that it is necessary to take these heteromers into ...
Functional CB1 cannabinoid receptors in human vascular endothelial cells. Jie LIU, Bin GAO, Faridoddin MIRSHAHI, Arun J. SANYAL ... Functional CB1 cannabinoid receptors in human vascular endothelial cells. Jie LIU, Bin GAO, Faridoddin MIRSHAHI, Arun J. SANYAL ... Functional CB1 cannabinoid receptors in human vascular endothelial cells Message Subject (Your Name) has forwarded a page to ... a selective CB1 receptor antagonist. Transfection of ECV304 cells with CB1 receptor antisense, but not sense, oligonucleotides ...
A novel CB1 receptor agonist lead series was identified using a high-throughput screening approach. The initial screen afforded ... soluble cannabinoid CB1 receptor. agonists. Julia M. Adam,*a Jim Cairns,a Wilson Caulfield,a Phillip Cowley,a Iain Cumming,a ... soluble cannabinoid CB1 receptor. agonists. J. M. Adam, J. Cairns, W. Caulfield, P. Cowley, I. Cumming, M. Easson, D. Edwards, ... A novel CB1 receptor agonist. lead series was identified using a high-throughput screening approach. The initial screen ...
Synthesis of long-chain amide analogs of the cannabinoid CB1 receptor antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4- ... Synthesis of long-chain amide analogs of the cannabinoid CB1 receptor antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4- ...
Effects of cannabinoid CB1 receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in ... Endocannabinoids modulate striatal dopamine activity via type 1 cannabinoid (CB(1)) receptors, and studies in rats and humans ... The present study explored the effects of CB(1) receptor ligands on oral dyskinesia induced by the dopamine D(1) receptor ... The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and ...
... and CB2 receptors were determined. In the 2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A second ... Several compounds in both series have CB, receptor ... were synthesized and their affinities for the cannabinoid CB, ... 2006). 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: New high affinity ligands for the cannabinoid CB1 and CB2 receptors. Bioorganic ... 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: New high affinity ligands for the cannabinoid CB1 and CB2 receptors. ...
BACKGROUND Cannabinoids exert a wide spectrum of effects in men including alterations in the reproductive system. To date, two ... two types of cannabinoid receptors have been cloned in humans, namely CB1 and CB2 belonging to the G protein-coupled receptor ... Source: Expression of functionally active cannabinoid receptor CB1 in the human prostate gland - Ruiz-Llorente - 2002 - The ... Although cannabinoids have functional and morphologic effects in the prostate gland, the expression of cannabinoid receptors in ...
Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions Message Subject (Your Name) ... Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions. Somnath Mukhopadhyay and ... Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions. Somnath Mukhopadhyay and ... Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions. Somnath Mukhopadhyay and ...
Activating Parabrachial Cannabinoid CB1 Receptors Selectively Stimulates Feeding of Palatable Foods in Rats Abstract The ... brainstem cannabinoids CB1 receptor eating feeding opioid parabrachial reward Feeding and energy balance are regulated by a ... Activating Parabrachial Cannabinoid CB1 Receptors Selectively Stimulates Feeding of Palatable Foods in Rats. Abstract. The ... brainstem cannabinoids CB1 receptor eating feeding opioid parabrachial reward Previous Section. Next Section. Introduction. ...
  • These results suggest that SR is an effective antagonist of the psychoactive effects of cannabinoids. (springer.com)
  • This effect was blocked by the CB1 receptor antagonist SR141716A (0.5 microM), and by phosphoinositide-3-kinase and phospholipase C inhibitors. (nih.gov)
  • SR141716A, a selective antagonist for CB1, inhibited the cannabinoid agonist-induced migratory responses in a concentration-dependent manner. (aspetjournals.org)
  • or on dopaminergic D1 receptor expressing neurons (D1CB1-/-)], and wild-type (WT) mice treated with CB1 antagonist/inverse agonist SR141716A (3mg/kg). (uni-muenchen.de)
  • CB1 receptor-binding sites were detected by the high-affinity antagonist radioligand [ 125 I]AM-251. (biochemj.org)
  • In ECV304 cells, both the highly potent synthetic cannabinoid agonist HU-210 and the endogenous ligand anandamide induce activation of mitogen-activated protein (MAP) kinase, and the effect of HU-210 was completely blocked, whereas the effect of anandamide was partially inhibited by SR141716A, a selective CB1 receptor antagonist. (biochemj.org)
  • The present study explored the effects of CB(1) receptor ligands on oral dyskinesia induced by the dopamine D(1) receptor agonist SKF81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. (sigmaaldrich.com)
  • The selective cannabinoid 1 receptor (CB1R) antagonist AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] prevented the response, demonstrating CB1R mediation of 2-AG-induced coupling. (420magazine.com)
  • 0.001) but CB 2 receptors antagonist (AM630, 1.25µg) had no effect. (scielo.br)
  • Using stably transfected Chinese Hamster Ovary cells expressing human CB1 we show here that cannabinoid treatment induces both phosphorylation and activation of mitogen-activated protein (MAP) kinases, and that these effects are inhibited by SR 141716A, a selective CB1 antagonist. (biochemj.org)
  • 14h has been described previously as a peripherally selective, high affinity CB1 receptor antagonist. (uncg.edu)
  • 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR-141716A (SR)). SR is a potent and a selective CB1 receptor antagonist and inverse agonist. (uncg.edu)
  • The effect of 30 nM of noladin ether was completely blocked by SR141716A, a selective CB1 antagonist. (arvojournals.org)
  • Rimonabant (SR141716), a CB1 receptor antagonist, blocks both the dopamine-releasing and the discriminative and rewarding effects of Delta(9)-THC in animals. (cannabis-marijuana.com)
  • Here we investigated the effects of CB 1 receptor antagonist rimonabant (SR141716A), which has recently been shown to have anti-atherosclerotic effects both in mice and humans, on PDGF-induced proliferation, migration, and signal transduction of human coronary artery smooth muscle cells (HCASMCs). (elsevier.com)
  • PDGF induced Ras and ERK 1/2 activation, while increasing proliferation and migration of HCASMCs, which were dose dependently attenuated by CB1 antagonist, rimonabant. (elsevier.com)
  • The aim of this study was to investigate the effects of AM251 (a selective CB1 antagonist) and JTE907 (a selective CB2 antagonist) on morphine analgesia and tolerance in rats. (cumhuriyet.edu.tr)
  • The selective CB1 antagonist, AM281 (0.5 microg/kg-1 i.p.) reversed effects of HU210 (10 and 30 microg/kg-1 i.p.) in both nociceptive and inflammatory models of hypersensitivity. (ox.ac.uk)
  • A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. (wikipedia.org)
  • Cannabidiol (CBD), a naturally occurring cannabinoid, is a non-competitive CB1/CB2 receptor antagonist. (wikipedia.org)
  • CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. (wikipedia.org)
  • The first specific CB1 receptor antagonist / inverse agonist was rimonabant, discovered in 1994. (wikipedia.org)
  • In conclusion, THCV behaves as a competitive CB 1 and CB 2 receptor antagonist. (thecannabisadvisory.com)
  • SR147778, a CB1 cannabinoid receptor antagonist, suppresses ethanol preference in chronically alcoholized Wistar rats. (uclouvain.be)
  • This study investigated the effect of the new CB1 cannabinoid receptor antagonist, SR147778, on ethanol preference in chronically alcoholized Wistar rats. (uclouvain.be)
  • Oral administration of Imidazole 24b blocked CP-55940-induced hypothermia, demonstrating cannabinoid CB(1) receptor antagonist efficacy in vivo. (scienceexchange.com)
  • [16] Another psychoactive cannabinoid present in Cannabis sativa is tetrahydrocannabivarin (THCV), but it is only found in small amounts and is a cannabinoid antagonist. (wikipedia.org)
  • In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. (biomedcentral.com)
  • CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). (strath.ac.uk)
  • The cannabinoid CB1 receptor antagonist Rimonabant stimulates 2-deoxyglucose uptake in skeletal muscle cells by regulating phosphatidylinositol-3-kinase activity. (unisa.it)
  • Exposure of differentiated L6 myotubes to the CB1 antagonist rimonabant (SR141716) selectively increased 2-deoxyglucose uptake (2-DG) in a time- and dose-dependent manner. (unisa.it)
  • Compounds SC4a , SN15b , SC33 and FG45a were found to decrease the SRE response induced by CB1 agonist CP55,940 (33 nM). (nih.gov)
  • In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of the CB1 agonist HU-210 on the VR1-mediated increase in intracellular Ca2+ ([Ca2+]i), a well-known response of the prototypical VR1 agonist capsaicin. (nih.gov)
  • The endogenous agonist of CB1 and VR1 receptors, anandamide, was more efficacious in inducing a VR1-mediated stimulation of [Ca2+]i in CB1-VR1-HEK cells than in VR1-HEK cells, and part of its effect on the former cells was blocked by SR141716A (0.5 microM). (nih.gov)
  • Pretreating cells with 100 ng/ml pertussis toxin eliminated the cannabinoid agonist-induced cell migration. (aspetjournals.org)
  • Some hCB1 receptors were constitutively active because the cannabinoid receptor inverse agonist SR 141617A enhanced the Ca 2+ current. (jneurosci.org)
  • Some hCB1 receptors also appear to be precoupled to G i/o -proteins because the cannabinoid agonist WIN 55,212-2 decreased the Ca 2+ current at a time when no G-proteins were available to couple to α 2 -adrenergic and somatostatin receptors. (jneurosci.org)
  • Those G-proteins trapped by the inverse agonist would be unavailable to couple to other receptors. (jneurosci.org)
  • We found that the mutation of aspartate to asparagine (CB1-D164N) abolished G-protein sequestration and constitutive receptor activity without disrupting agonist-stimulated activity. (jneurosci.org)
  • A novel CB1 receptor agonist lead series was identified using a high-throughput screening approach. (rsc.org)
  • This led to the discovery of Org 28611, a potent, water soluble CB1 receptor agonist , which was selected for clinical evaluation as a potential intravenous analgesic agent. (rsc.org)
  • Nonetheless, infusions of a synthetic cannabinoid agonist into the fourth ventricle modestly increased feeding (Miller et al. (420magazine.com)
  • In addition, pretreatment with CB1/CB2 selective antagonists, AM251 and AM630, prior to JWH-015 and Win55,212-2 treatments, attenuated the agonist-mediated inhibition of in vitro chemotaxis and chemoinvasion. (aacrjournals.org)
  • These effects were receptor mediated, as pretreatment with CB1/CB2 antagonists abrogated CB1/CB2 agonist-mediated effects on tumor growth and metastasis. (aacrjournals.org)
  • John C. Ashton* and Robert J. Hancox, "The Case for Cannabinoid CB1 Receptors as a Target for Bronchodilator Therapy for β-agonist Resistant Asthma", Current Drug Targets (2018) 19: 1344. (eurekaselect.com)
  • The aim of this study was to evaluate the impact of ACEA (arachidonyl-2′-chloroethylamide-a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells׳ proliferation and differentiation in the mouse brain. (deepdyve.com)
  • In this research, the effects of an L-type calcium channel blocker (verapamil) and a cannabinoid CB1 receptor agonist (ACEA) on pentylenetetrazole-induced seizure model in mice were studied. (sid.ir)
  • The results showed that inhibition of L-type calcium channel by verapamil did not affect the anti-seizure properties of cannabinoid CB1 receptor agonist. (sid.ir)
  • The results demonstrate for the first time that administration of noladin ether, an endocannabinoid agonist selective for the CB1 receptor, increases aqueous humor outflow facility. (arvojournals.org)
  • This will be examined on an unbiased whole-brain basis, using agonist-stimulated [35S]GTPgammaS and [3H]ligand autoradiography to assess CB1-mediated G-protein activity and receptors, respectively. (grantome.com)
  • The affinity of the cannabinoid agonist CP55,940 was unaffected by the F3.25A, F3.36A, W5.43A, or W6.48A mutations, making CP55,940 an appropriate choice as the radioligand for binding studies. (kennesaw.edu)
  • The C-terminus of CB2 receptors appears to play a critical role in the regulation of ligand-induced receptor desensitization and downregulation following repeated agonist application, perhaps causing the receptor to become less responsive to particular ligands. (wikipedia.org)
  • The analgesic effects of morphine (5 mg/kg), ACEA (a CB1 receptor agonist, 5 mg/kg), JWH-015 (a CB2 receptor agonist, 5 mg/kg), AM251 (1 mg/kg) and JTE907 (5 mg/kg) were considered at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. (cumhuriyet.edu.tr)
  • The cannabinoid agonist, HU210 has been evaluated in vivo in nociceptive and inflammatory pain models in the rat. (ox.ac.uk)
  • 2003). Although all purinergic receptors involved in these effects have not yet been elucidated the P2X receptor agonist BzATP decreases the expression of several LPS-stimulated inflammatory mediators (Boucsein et al. (technumber.com)
  • Because BzATP is an agonist of several P2X receptor subtypes (Burnstock and Knight 2004) and the mechanisms underlying the inhibitory effects of BzATP on microglial gene transcription are not known the first hypothesis we tested in the present studies was that P2X7 receptors in specific mediate the inhibitory effects of BzATP on Cladribine LPS-stimulated iNOS gene expression in microglia. (technumber.com)
  • Yamamura, Henry I. / AM630 is an inverse agonist at the human cannabinoid CB 1 receptor . (elsevier.com)
  • THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant. (wikipedia.org)
  • The use of the cannabinoid agonist, THC, in its many preparations to enhance appetite is a well known fact. (wikipedia.org)
  • [13] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors. (wikipedia.org)
  • Characterization of a novel and selective cannabinoid CB1 receptor inverse agonist, Imidazole 24b, in rodents. (scienceexchange.com)
  • We document in vitro and in vivo effects of a novel, selective cannabinoid CB(1) receptor inverse agonist, Imidazole 24b (5-(4-chlorophenyl)-N-cyclohexyl-4-(2,4-dichlorophenyl)-1-methyl-imidazole-2-carboxamide). (scienceexchange.com)
  • in vitro, it is a receptor inverse agonist at both cannabinoid CB(1) and CB(2) receptors as it causes a further increase of forskolin-induced cAMP increase. (scienceexchange.com)
  • Using ex vivo autoradiography, Imidazole 24b resulted in dose-dependent increases in brain cannabinoid CB(1) receptor occupancy (RO) at 2h post-dosing in rats, indicating that approximately 50% receptor occupancy is sufficient for attenuation of receptor agonist-induced hypothermia. (scienceexchange.com)
  • However, this effect could not be mimicked by inhibiting constitutive activity or receptor activation, either by expressing mutant receptors that lack these properties or by treatment with CB1 receptor antagonists possessing inverse agonist activity. (dundee.ac.uk)
  • We have previously reported that intravesical administration of a cannabinoid agonist reduces the electrical activity of bladder afferents under normal conditions. (biomedcentral.com)
  • This study was aimed to assess the effects of intravesical administration of a cannabinoid agonist on the discharges of afferent fibers in inflamed bladders ex vivo . (biomedcentral.com)
  • Local treatment with a non selective cannabinoid agonist (AZ12646915) significantly reduced the afferent activity at intravesical pressures above 20 mmHg. (biomedcentral.com)
  • Also, TRPV1 positive fibers were found to co-express CB 1 , supporting the hypothesis of a direct action of the cannabinoid agonist on nociceptive afferents. (biomedcentral.com)
  • The purpose of the present study was to assess the effect of intravesical administration of a cannabinoid agonist on afferent bladder activity after an acute inflammation induced by cyclophosphamide (CYP). (biomedcentral.com)
  • In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. (scienceopen.com)
  • A single injection of a CB1 cannabinoid receptor agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. (scienceopen.com)
  • The primary endogenous agonist of the human CB 1 receptor is anandamide . (wikipedia.org)
  • In addition, the analgesic and catatonic effects were reversed by the cannabinoid receptor type 1 (CB1) inverse agonist rimonabant. (wikipedia.org)
  • Mansbach RS (1991) Effects of NMDA receptor ligands on sensorimotor gating in the rat. (springer.com)
  • The actions of cannabinoids are also regulated by the endocannabinoid system (ECS) which includes enzymes involved in synthesis, uptake and degradation of endogenous cannabinoid ligands, and the CB1 and CB2 receptors. (frontiersin.org)
  • Endocannabinoids modulate striatal dopamine activity via type 1 cannabinoid (CB(1)) receptors, and studies in rats and humans suggest beneficial effects of CB(1) ligands on EPS. (sigmaaldrich.com)
  • To understand how structurally distinct ligands regulate CB 1 receptor interactions with Gi1, Gi2, and Gi3, we quantified the Gαi and βγ proteins that coimmunoprecipitate with the CB 1 receptor from a detergent extract of N18TG2 membranes in the presence of ligands. (aspetjournals.org)
  • These ligand-selective G protein responses imply that multiple conformations of the receptor could be evoked by ligands to regulate individual G proteins. (aspetjournals.org)
  • In addition, biased mutants developed here should assist structure-based drug design of CB1 receptor ligands with ß-arrestin functional selectivity. (uncg.edu)
  • The major targets of cannabinoid ligands are cannabinoid (CB)1 and CB2 receptors. (arvojournals.org)
  • Findings from both clinical and preclinical studies suggest that ligands blocking CB1 receptors offer a novel approach for patients suffering from drug dependence that may be efficacious across different classes of abused drugs. (cannabis-marijuana.com)
  • Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG activates the MAPK-ERK pathway, while noladin inhibits adenylyl cyclase. (wikipedia.org)
  • Introduction Many immune properties of microglia CNS-resident phagocytic immune cells are controlled by P2 purinergic receptors for which adenine nucleotides are the endogenous ligands. (technumber.com)
  • The endogenous cannabinoid system includes cannabinoid receptors, their endogenous ligands (endocannabinoids) and enzymes for their synthesis and degradation. (wikipedia.org)
  • The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). (springer.com)
  • Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. (springer.com)
  • This rapid decline in CB1-deficient animals is accompanied by a loss of neurons in the CA1 and CA3 regions of the hippocampus. (pnas.org)
  • Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and dorsal root ganglia. (nih.gov)
  • CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). (frontiersin.org)
  • The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important. (frontiersin.org)
  • At the electron microscopic level CB1 receptor was restricted to neurons. (nih.gov)
  • The existence and function of the CB2 receptors in the neurons has always been controversial. (innovations-report.com)
  • This new research now offers two relevant conclusions: in the first place, the expression of CB2 as a protein in the neurons is confirmed and, in the second place, it is shown that the CB2 receptors may be a new pharmacological target for the modulation of the effect of cannabinoids through the CB1 receptor, forming CB1-CB2 heteromers which are expressed in the brain. (innovations-report.com)
  • Human CB1 cannabinoid receptors were expressed in superior cervical ganglion (SCG) neurons by microinjection of hCB1 cDNA. (jneurosci.org)
  • Although type 1 cannabinoid receptors (CB 1 Rs) are expressed abundantly throughout the brain, the presence of type 2 cannabinoid receptors (CB 2 Rs) in neurons is still somewhat controversial. (springer.com)
  • Taking advantage of newly designed CB 1 R and CB 2 R mRNA riboprobes, we demonstrate by PCR and in situ hybridization that transcripts for both cannabinoid receptors are present within labeled pallidothalamic-projecting neurons of control and MPTP-treated macaques, whereas the expression is markedly reduced in dyskinetic animals. (springer.com)
  • Given that mRNA for the two receptors was present in the same neurons, and an in situ proximity ligation assay (PLA) detected the localization of CB 1 Rs, CB 2 Rs and CB 1 R-CB 2 R heteromers in the cell somata of projection neurons. (springer.com)
  • Cannabinoids play a role in setting the threshold of excitability of neurons through the presynaptic CB1 receptor. (sid.ir)
  • Calcium channels, both in the cell membrane and inside the cytoplasm of neurons, are affected by cannabinoid receptors. (sid.ir)
  • We found reduced Npy expression and Npy type 1 receptor (Npy1r) signaling, and decreased expression of the cannabinoid type 1 receptor (CB1) in the cingulate cortex of CUS mice specifically in low CB1-expressing neurons. (diagenode.com)
  • Cannabinoids protect cortical neurons from ischemic injury by interacting with CB1 receptors. (unthsc.edu)
  • Western blotting and immunohistochemistry showed that CB1 expression on neurons was increased in the arterial boundary zone of the cortical mantle, beginning by 2 hours and persisting for 72 hours or more after ischemia. (unthsc.edu)
  • Originally it was thought that the CB2 receptor was only expressed in peripheral tissue while the CB1 receptor is the endogenous receptor on neurons. (wikipedia.org)
  • We found that CB1 mRNA and protein are reduced in schizophrenia, which may represent a compensatory mechanism to increase GABA transmission from perisomatic-targeting CCK neurons with impaired GABA synthesis. (pitt.edu)
  • We conclude that reductions in the expression of the CB1 receptor mRNA and protein in CCK neurons represent a novel neuropathological entity in the DLPFC of individuals with schizophrenia. (pitt.edu)
  • The proper functioning of striatal neurons relies critically on metabotropic receptors. (uea.ac.uk)
  • Specifically, our data unveil that the A2AR-CB1R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. (uea.ac.uk)
  • In central neurons, the cell-surface distribution of cannabinoid receptor subtype-1 (CB1) is highly polarized toward axons and is associated with synaptic terminals, in which it is well-positioned to modulate neurotransmitter release. (dundee.ac.uk)
  • We have investigated further the mechanisms that underlie CB1 receptor axonal polarization in hippocampal neurons and found that constitutive activity is not an essential requirement for this process. (dundee.ac.uk)
  • We demonstrate that the cell-surface distribution of an N-terminally tagged, fluorescent CB1 receptor fusion-protein is almost exclusively localized to the axon when expressed in cultured hippocampal neurons. (dundee.ac.uk)
  • CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. (biomedcentral.com)
  • It strikes as much as the neurons to connect to cannabinoid receptors there. (randomeyes.net)
  • Once there, the cannabinoids are able to control what occurs the following time the neurons activate. (randomeyes.net)
  • Although the role of the habenula, a central region of the brain, in this phenomenon has received a great deal of attention in recent years, the same is not true of the endogenous cannabinoid system of the habenular neurons, on which Giovanni Marsicano and his team (particularly Edgar Soria-Gomez) have focused. (eurekalert.org)
  • dopamine neurons by an action on cannabinoid CB1 receptors. (usdoj.gov)
  • SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has recently been reported to reverse biochemical, physiological and behavioral effects induced by cannabinoid agonists. (springer.com)
  • Our data suggest that in cells co-expressing both CB1 and VR1 receptors, pre-treatment with CB1 agonists inhibits or stimulates VR1 gating by capsaicin depending on whether or not cAMP-mediated signalling has been concomitantly activated. (nih.gov)
  • HU-210, WIN55212-2, and anandamide, three cannabinoid agonists with distinct chemical structures, induced migration of human embryonic kidney 293 cells stably transfected with human CB1 gene, but not 293 cells transfected with an empty expression vector. (aspetjournals.org)
  • These data demonstrate that cannabinoid agonists are able to induce chemotaxis and chemokinesis, and that these migratory responses are mediated by G protein-coupled, CB1 cannabinoid receptors. (aspetjournals.org)
  • Classical cannabinoid agonists (structures shown in Table 1 ) bind to and activate cannabinoid receptors 1 and 2 (CB1, CB2) that modulate signal transduction cascades to produce various physiological and pathological outcomes. (frontiersin.org)
  • Furthermore, we have shown that the treatment of NSCLC cell lines (A549 and SW-1573) with CB1/CB2- and CB2-specific agonists Win55,212-2 and JWH-015, respectively, significantly attenuated random as well as growth factor-directed in vitro chemotaxis and chemoinvasion in these cells. (aacrjournals.org)
  • Upon further elucidation into the molecular mechanism, we observed that both CB1 and CB2 agonists inhibited phosphorylation of AKT, a key signaling molecule controlling cell survival, migration, and apoptosis, and reduced matrix metalloproteinase 9 expression and activity. (aacrjournals.org)
  • However, the unformed knowledge in drug-receptor interactions at the molecular level, and in the CB1 receptor signaling properties, has hampered the transition of many synthesized CB1 receptor agonists and antagonists to clinical use. (uncg.edu)
  • Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration. (wikipedia.org)
  • And Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. (wikipedia.org)
  • Once cannabinoid receptors had been discovered, it became important to establish whether their agonists occur naturally in the body. (wikipedia.org)
  • Endocannabinoids are eicosanoids acting as agonists for cannabinoid receptors, and they occur naturally in the body. (wikipedia.org)
  • CB1 antagonists produce inverse cannabimimetic effects that are opposite in direction from those produced by agonists for these receptors. (wikipedia.org)
  • [16] Activation of the MAPK-ERK pathway by CB 2 receptor agonists acting through the G βγ subunit ultimately results in changes in cell migration [17] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1). (wikipedia.org)
  • These findings suggest that selective cannabinoid CB(1) receptor inverse agonists such as Imidazole 24b have potential for the treatment of obesity. (scienceexchange.com)
  • Systemic administration of cannabinoid agonists is known to reduce pain induced by bladder inflammation and to modulate cystometric parameters in vivo . (biomedcentral.com)
  • Although some of these cystometric and behavioral effects of cannabinoids could involve the afferent component of the bladder, the precise contribution of afferent effects is difficult to ascertain because of the techniques used and the systemic administration of the agonists. (biomedcentral.com)
  • However, nothing is known about the responses to cannabinoid agonists of afferents from inflamed bladders. (biomedcentral.com)
  • This entry was posted in Asthma , Endocannabinoid System and tagged agonists , anti-inflammatory , cannabinoid receptors , Cannabinoids , CB1 by David . (thctotalhealthcare.com)
  • THE ANATOMICAL RECORD 293:1425-1432 (2010) Temporal and Spatial Distribution of the Cannabinoid Receptors (CB1, CB2) and Fatty Acid Amide Hydroxylase in the Rat Ovary P. BAGAVANDOSS* AND S. GRIMSHAW Department of Biological Sciences, Kent State University at Stark, North Canton, Ohio ABSTRACT Although the effects of D9-tetrahydrocannabinol (THC) on ovarian physiology have been known for many decades, its mechanism of action in the rat ovary remains poorly understood. (docme.ru)
  • abstract = "The present investigation examines WIN 55,212-2 and AM630 at the cloned human cannabinoid CB1 receptor stably expressed in Chinese hamster ovary (CHO) cells. (elsevier.com)
  • Cannabinoid-1 receptor (CB1R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and human obesity, but their therapeutic potential is limited by neuropsychiatric side effects. (jci.org)
  • The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. (sigmaaldrich.com)
  • T his review examines the development of cannabinoid CB1 receptor antagonists as a new class of therapeutic agents for drug addiction. (cannabis-marijuana.com)
  • Cannabinoid CB1 and CB2 receptor antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance. (cumhuriyet.edu.tr)
  • The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. (wikipedia.org)
  • This revived the research on cannabinoid receptor antagonists which were expected to help answer these questions. (wikipedia.org)
  • Cannabinoid 1 (CB 1 ) receptor antagonists exhibit pharmacological properties favorable for the treatment of obesity and other related metabolic disorders. (biomedcentral.com)
  • Despite a large body of knowledge on cannabinoid receptor antagonists little data exist on the quantitative pharmacology of this therapeutic class of drugs. (biomedcentral.com)
  • The observation that CB 1 receptor antagonists may be useful as drugs for the management of obesity and metabolic disease was made in 1997 when Aronne and colleagues reported that SR141716A (rimonabant) selectively inhibited sucrose consumption relative to normal chow consumption in male rats [ 6 ]. (biomedcentral.com)
  • Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. (nih.gov)
  • To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. (nih.gov)
  • CB1 receptors (CB1R) mediate the psychoactive effects of delta9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and therapeutic effects of cannabinoids (CBs) in the CNS. (grantome.com)
  • Chronic CB effects occur by G-protein receptor kinase/beta-arrestin mediated uncoupling of CB1R from Gproteins (desensitization) and/or reduction in CB1R density (downregulation). (grantome.com)
  • Further, because region-specific adaptation is dependent on interaction with different regulatory proteins, based on their anatomical co-distribution with CB1 R, we hypothesize that CB1R adaptation will be decreased in Beta-arrestin-2 null mice. (grantome.com)
  • Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. (uea.ac.uk)
  • The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. (frontiersin.org)
  • Thus, the CB1 cannabinoid receptor functions to modulate neuronal excitability and neurotransmitter release. (jneurosci.org)
  • Moreover, CB1 receptors specifically modulate social investigation of female mice in a cell-specific manner. (uni-muenchen.de)
  • Cannabinoid CB1 receptors are expressed in this brain reward circuit and modulate the dopamine-releasing effects of Delta(9)-THC and nicotine. (cannabis-marijuana.com)
  • Cannabinoids may modulate cell proliferation and migration in various cell types through cannabinoid receptors. (elsevier.com)
  • 2003). Further studies foundthat EA pretreatment could modulate the endocannabinoidsystem by upregulating the production of the endocannabi-noids, including 2-arachidonylglycerol (2-AG) and N-arach-idonoylethanolamine-anandamide (AEA), which cause protec-tion through cannabinoid CB1 receptors (Wang et al. (pdfslide.tips)
  • Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis -derived molecules. (frontiersin.org)
  • The role of the cannabinoid receptor in brain function is thought to be related to the effects of marijuana ( Cannabis sativa ), which include euphoria, hypothermia, analgesia, appetite stimulation, and memory impairment. (jneurosci.org)
  • Marijuana consists of a mixture of leaves, stems, and flowering tops of Cannabis plants selectively bred to produce high levels of Δ 9 -tetrahydrocannabinol (THC or (−)-trans-Δ 9 -THC) and several other psychoactive cannabinoids. (hindawi.com)
  • It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol, the active agent in cannabis, and other phytocannabinoids (plant cannabinoids). (wikipedia.org)
  • The effects of cannabis are mediated by the brain cannabinoid 1 (CB1) receptor, which in the rodent, is heavily localized to certain inhibitory axon terminals and, when activated, inhibits GABA release. (pitt.edu)
  • Cannabinoid pharmacology has been intensely studied because of cannabis' pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. (tind.io)
  • The effects of cannabis are caused by the chemical compounds in the plant, including cannabinoids , such as tetrahydrocannabinol (THC), which is only one of more than 100 different cannabinoids present in the plant. (wikipedia.org)
  • Different plants of the genus Cannabis contain different and often unpredictable concentrations of THC and other cannabinoids and hundreds of other molecules that have a pharmacological effect, [2] [3] so that the final net effect cannot reliably be foreseen. (wikipedia.org)
  • [4] [5] Cannabidiol (CBD), another cannabinoid found in cannabis in varying amounts, has been shown to alleviate the adverse effects of THC that some consumers experience. (wikipedia.org)
  • The most prevalent psychoactive substances in cannabis are cannabinoids , most notably THC . (wikipedia.org)
  • The essential oil of cannabis contains many fragrant terpenoids which may synergize with the cannabinoids to produce their unique effects. (wikipedia.org)
  • Cannabidiol (CBD) is the main non-psychotropic compound of the plant cannabis sativa and belongs to the group of exogenous cannabinoids [ 15 ]. (biomedcentral.com)
  • Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. (cdc.gov)
  • The Cannabis sativa plant, also known as marijuana, contains compounds called cannabinoids, which can act on the brain to affect mood or consciousness. (nih.gov)
  • Cannabinoids come from two distinct places - the physique, which produces naturally occurring endocannabinoids, and the cannabis plant, which produces phytocannabinoids. (randomeyes.net)
  • Therefore the results of cannabis and exogenous cannabinoids, of both plant and artificial origin, are in many instances totally different from, or even reverse to, those of the EC system. (randomeyes.net)
  • [13] The CB 1 receptor is activated by cannabinoids , generated naturally inside the body ( endocannabinoids ) or introduced into the body as cannabis or a related synthetic compound. (wikipedia.org)
  • These receptors, the activity of which is normally regulated by endocannabinoids - the body's own molecules - are the target of the main psychoactive components of cannabis. (eurekalert.org)
  • Mesenteric vasodilator effect of anandamide ( A ) and abnormal cannabidiol ( B ) in the absence (●) or presence of SR141716A (1 μM ▵ or 5 μM ○) in CB1 +/+ ( Left ) and CB1 −/− mice ( Right ). (pnas.org)
  • This provides more definitive evidence for the involvement of CB1 receptors in MAP kinase activation and suggests that anandamide may also activate MAP kinase via an additional, CB1 receptor-independent, SR141716A-resistant mechanism. (biochemj.org)
  • 1995). Recently, the presence of both CB1 and CB2 receptors as well as anandamide and its biosynthetic enzyme N-acylphosphatidylethanolamine-phospholipase D and the degrading enzyme fatty acid amide hydrolase (FAAH) has been demonstrated in the human ovary (ElTalatini et al. (docme.ru)
  • Five recognized cannabinoids are produced endogenously: arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine, as well as N-arachidonoyl-dopamine (NADA). (wikipedia.org)
  • This search led to the discovery of the first endogenous cannabinoid (endocannabinoid), anandamide (arachidonoyl ethanolamide). (wikipedia.org)
  • CB1 is activated in the body by a molecule called anandamide, and it's also the same receptor that cannabinoids activate. (wired.com)
  • Could be a receptor for anandamide. (abcam.com)
  • C ) in the absence (●) and presence of 3 μg/g SR141716A (○) on mean arterial blood pressure in pentobarbital-anesthetized CB1 +/+ ( Left ) and CB1 −/− ( Right ) mice. (pnas.org)
  • Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. (nih.gov)
  • Also, when all mice lines were submitted to different social tasks, involving male or female as the stimulus subject, GluCB1-/- mice showed reduced interest for the social stimulus, as CB1-/- or WT treated with SR141716A mice. (uni-muenchen.de)
  • Transfection of ECV304 cells with CB1 receptor antisense, but not sense, oligonucleotides caused the same pattern of inhibition as SR141716A. (biochemj.org)
  • In this study, postmortem brain tissues from a cohort of prospectively assessed, neuropathologically confirmed AD patients and aged controls were used to measure CB1 receptors by immunoblotting, and a subset of subjects also had [(3)H]SR141716A binding. (ox.ac.uk)
  • Compton DR, Johnson MR, Melvin LS, Martin BR (1992) Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents. (springer.com)
  • The pharmacological actions of THC result from its activity at the cannabinoid CB1 receptor, located mainly in the central nervous system, the lungs, liver, and kidneys, and the CB2 receptor, mainly expressed in cells of the immune system and in hematopoietic cells. (hindawi.com)
  • 1993), and proteins modulating their synthesis and inactivation (Piomelli, 2003) has afforded considerable pharmacological precision in elucidating various molecular, cellular, and behavioral actions of the cannabinoid system. (420magazine.com)
  • WIN 55212.2, in agreement with the pharmacological profile of CB1. (biochemj.org)
  • CB2 was cloned in 1993 by a research group from Cambridge looking for a second cannabinoid receptor that could explain the pharmacological properties of tetrahydrocannabinol. (wikipedia.org)
  • These findings raised further questions about the pharmacological and physiological role of the cannabinoid system. (wikipedia.org)
  • It was then discovered that the blockage of the CB1 receptor represented a new pharmacological target. (wikipedia.org)
  • Silencing of CB1 in mice (through genetic or pharmacological means) has also been shown to cause the retention of a large number of embryos in the oviduct, leading to pregnancy failure. (sciencemag.org)
  • Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. (frontiersin.org)
  • Consistent with this discovering, mice without the CB1 receptor show enhanced reminiscence and long-time period potentiation indicating that the endocannabinoid system might play a pivotal function within the extinction of old memories. (randomeyes.net)
  • We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. (frontiersin.org)
  • In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. (frontiersin.org)
  • Cannabinoid CB1 receptor mRNA was detected using reverse transcription-polymerase chain reaction (RT-PCR) in endothelial cells from human aorta and hepatic artery and in the ECV304 cell line derived from human umbilical vein endothelial cells. (biochemj.org)
  • Both mRNA for CB1 and the corresponding protein are expressed in the human prostate gland at a level comparable with the receptor expressed in cerebellum. (420magazine.com)
  • Over a decade ago, the CB1 receptor mRNA has been shown to be present in the human ovary (Galiegue et al. (docme.ru)
  • Initial investigation of CB2 receptor expression patterns focused on the presence of CB2 receptors in the peripheral tissues of the immune system, and found the CB2 receptor mRNA in the spleen, tonsils, and thymus gland. (wikipedia.org)
  • In addition, we explored the potential relationship between CB1 receptor signaling and altered GABA neurotransmission in schizophrenia by evaluating CB1 receptor mRNA and protein expression in the DLPFC of subjects with schizophrenia. (pitt.edu)
  • Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets. (frontiersin.org)
  • The CB1 cannabinoid receptor is one of the most abundant receptors in the brain and it helps to regulate movement, as well as functioning as a therapeutic target for the treatment of pain, inflammation and Parkinson's disease, and it alleviates some side effects in cancer patients. (innovations-report.com)
  • These changes may be of interest for further research about the therapeutic effects of cannabinoids in glial tumors. (420magazine.com)
  • Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC. (aacrjournals.org)
  • These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC. (aacrjournals.org)
  • Many potential therapeutic applications targeting the CB1 receptor are under investigation. (uncg.edu)
  • Cannabinoids are well known for their psychotropic properties, as well as for their therapeutic potential. (arvojournals.org)
  • Our findings suggest that epigenetic alterations in the Npy and CB1 genes represent one of the potential mechanisms contributing to the emotional imbalance induced by CUS in mice, and that the Npy and eCB systems may represent therapeutic targets for the treatment of psychopathologies associated with or triggered by chronic stress states. (diagenode.com)
  • Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD. (ox.ac.uk)
  • These findings are consistent with a neuroprotective role for endogenous cannabinoid signaling pathways and with a potential therapeutic role in stroke for drugs that activate CB1 receptors. (unthsc.edu)
  • Activation of cannabinoid receptors could be a new therapeutic approach for the treatment of skin tumors. (greenmedinfo.com)
  • Understanding how these chemicals bind to the CB 1 receptor will help guide the design of new medications and provide insight into the therapeutic promise of the body's cannabinoid system. (nih.gov)
  • As a consequence, the endogenous cannabinoid system of the habenula might represent a new therapeutic target in the management of these conditions. (eurekalert.org)
  • During the last years, several studies have demonstrated that cannabinoids induce apoptosis of glioma cells and inhibit angiogenesis of gliomas in vivo. (420magazine.com)
  • Such people tend to have higher adiponectin , higher growth hormone (cannabinoids inhibit growth hormone release [ 2 ]), lower triglycerides , higher HDL, lower insulin resistance , lower CRP and higher TSH , but not higher T4 / T3 [cannabinoids decrease TSH 3 ]. (selfhacked.com)
  • Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits. (wikipedia.org)
  • Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit the accumulation of cyclic adenosine monophosphate within cells. (wikipedia.org)
  • CB1 receptors are coupled through Gi/o proteins and inhibit adenylyl cyclase and activate mitogen-activated protein (MAP) kinase. (wikipedia.org)
  • In addition, CB1 receptors inhibit presynaptic N- and P/Q-type calcium channels and activate inwardly rectifying potassium channels. (wikipedia.org)
  • [13] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB 2 receptors. (wikipedia.org)
  • The CB 1 receptor is expressed pre-synaptically at both glutaminergic and GABAergic interneurons and, in effect, acts as a neuromodulator to inhibit release of glutamate and GABA . (wikipedia.org)
  • Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. (sciencemag.org)
  • The ultrastructural localization of the CB1 receptor suggests that it modulates neuronal excitability by both pre- and postsynaptic mechanisms. (nih.gov)
  • However, the role of CB1 receptor is still unclear and its localization on different neuronal subpopulations may produce distinct outcomes. (uni-muenchen.de)
  • Bernardes Terzian, Ana Luisa (2014): Behavioral phenotypes of mice lacking cannabinoid CB1 receptors in different neuronal subpopulations: focus on sex-related social interest. (uni-muenchen.de)
  • However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca(2+)-binding proteins (CaBPs) is still unknown. (sigmaaldrich.com)
  • The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions. (sigmaaldrich.com)
  • It has been reported that concurrent activation of D 2 receptors and CB 1 receptors, in primary striatal neuronal culture, promotes functional CB 1 receptor coupling to Gα s resulting in elevations in intracellular cyclic AMP levels. (aspetjournals.org)
  • In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties. (deepdyve.com)
  • Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo. (ox.ac.uk)
  • BzATP also attenuates neuronal death induced by LPS conditioned medium and P2X7 receptors are required for this effect. (technumber.com)
  • Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. (biomedcentral.com)
  • We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells. (biomedcentral.com)
  • This study shows that stimulation of cannabinoid CB 1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism. (thctotalhealthcare.com)
  • CB 1 cannabinoid (CB 1 ) and D 2 dopamine (D 2 ) receptors are known to couple to the G protein Gα i/o . (aspetjournals.org)
  • With its location at presynaptic termini, it regulates the function of other receptors, including the dopamine, serotonin, GABA, opioid and glutamate receptors. (uncg.edu)
  • Because it is known that CB1 cannabinoid receptors are coupled to pertussis toxin-sensitive G proteins, we proposed that CB1 may mediate cell migration. (aspetjournals.org)
  • Its psychoactive substances act by interacting with proteins from the membrane of the cells which are their CB1 and CB2 receptors. (innovations-report.com)
  • We tested the hypothesis that human CB1 cannabinoid receptors (hCB1) can sequester G i/o -proteins from a common pool and prevent other receptors from signaling. (jneurosci.org)
  • These results suggest that both the active and inactive states of the hCB1 receptor can sequester G i/o -proteins from a common pool. (jneurosci.org)
  • We predicted that hCB1 receptors would deplete a pool of pertussis toxin-sensitive G-proteins such that signaling by other pertussis toxin-sensitive G-protein-coupled receptors would be disrupted. (jneurosci.org)
  • We found that truncation of the distal C-terminal tail of the CB1 receptor (CB1-417) enhanced both the constitutive activity and the ability of the receptor to sequester G-proteins. (jneurosci.org)
  • The CB1-D164N mutation shifts the receptor into an inactive R state upcoupled from G-proteins, whereas the C-terminal truncation (CB1-417) shifts the receptor into the active R*G GTP state. (jneurosci.org)
  • Thus the distal C-terminal tail acts to constrain the receptor from activating G-proteins, whereas the aspartate (D2.50) in the second transmembrane domain stabilizes the receptor in both the inactive RG GDP state and the active R*G GTP state. (jneurosci.org)
  • We predicted that removal of the distal C-terminal tail (CB1-417) would enhance both the constitutive activity and the ability of the CB1 cannabinoid receptor to sequester G-proteins. (jneurosci.org)
  • We predicted that the CB1-D164N mutation would destabilize G-protein coupling and block the ability of the CB1 receptor to sequester G-proteins and to adopt a constitutively active conformation. (jneurosci.org)
  • We found that the CB1-D164N mutant receptor was not constitutively active and could not sequester G-proteins. (jneurosci.org)
  • Immunofluorescence and in vitro [35S]GTPγS autoradiography of rat tissue sections containing the PBN revealed the presence of cannabinoid receptors and their functional capability to couple to their G-proteins after incubation with the endocannabinoid 2-arachidonoyl glycerol (2-AG). (420magazine.com)
  • Localization of the cannabinoid CB1 receptor and the 2-AG synthesizing (DAGLα) and degrading (MAGL, FAAH) enzymes in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus. (sigmaaldrich.com)
  • As the effects of cannabinoids rely on CB(1) and CB(2) receptors activation, the aim of the present study was to investigate both receptors protein expression in cellular membrane homogenates of human glial tumors using specific antibodies raised against these proteins. (420magazine.com)
  • including its structure, drugs that act at the CB1 receptor, G-protein and ß-arrestin mediated signaling pathways, as well as, CB1 receptor regulation by other proteins. (uncg.edu)
  • Research suggests that the majority of CB 1 receptors are coupled through G i/o proteins. (wikipedia.org)
  • Alternatively, in some rare cases CB 1 receptor activation may be coupled to G s proteins, which stimulate adenylate cyclase . (wikipedia.org)
  • The CB1 locus encodes an integral membrane-bound GTP-binding protein-coupled receptor (GPCR) possessing seven transmembrane domains and belonging to the rhodopsin-like superfamily of GPCR proteins. (sciencemag.org)
  • The most striking differences were high levels of CB1 receptor in the monkey substantia nigra pars compacta, cerebellar Purkinje cells, and the principal cells of the hippocampus, while few receptors were found in the globus pallidus or substantia nigra pars reticulata. (nih.gov)
  • For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. (sigmaaldrich.com)
  • NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus. (sysy.com)
  • Differential role of GABAA receptors and neuroligin 2 for perisomatic GABAergic synapse formation in the hippocampus. (sysy.com)
  • The cannabinoid system is very highly concentrated in the hypothalamus , basal ganglia , and the hippocampus, which are part of the limbic system. (selfhacked.com)
  • We found that CB1 receptor levels in were unchanged AD in the brain regions assessed (frontal cortex, anterior cingulate gyrus, hippocampus, caudate nucleus). (ox.ac.uk)
  • Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. (ac.be)
  • Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. (strath.ac.uk)
  • This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory. (strath.ac.uk)
  • To study the effects of 2-arachidonyl glyceryl ether (noladin ether), an endocannabinoid ligand selective for cannabinoid (CB)1 receptor, on aqueous humor outflow facility, to investigate the involvement of trabecular meshwork CB1 receptors and the p42/44 MAP kinase signaling pathway and to explore the cellular mechanisms of noladin ether-induced changes of outflow facility. (arvojournals.org)
  • The data also show that noladin ether-induced enhancement of outflow facility is mediated through the trabecular meshwork CB1 receptor, with an involvement of p42/44 MAP kinase signaling pathway and changes in actin cytoskeletons. (arvojournals.org)
  • Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. (nature.com)
  • To achieve the scientific goals, protein modeling will be utilized for the study the ligand-CB1 receptor-Galphai complex under the supervision of computational and pharmacology experts. (grantome.com)
  • We have combined quantitative pharmacology and ex vivo CB 1 receptor occupancy data to assess concentration/effect relationships in food intake, energy expenditure and weight loss studies. (biomedcentral.com)
  • Rimbonant can also have effects that are not all mediated through CB1 receptors, as I found out during the course of my Ph.D. But it is a neat little study, and one that expands our understanding of the pharmacology of placebos, to the degree such a thing is possible. (wired.com)
  • As is commonly seen in G protein-coupled receptors, the CB2 receptor has seven transmembrane spanning domains, a glycosylated N-terminus, and an intracellular C-terminus. (wikipedia.org)
  • Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. (wikipedia.org)
  • We report the results of a search for model-based relationships between hCB1 and hCB2 receptor binding affinity and molecular structure for a group of 1-aryl-5-(1-H-pyrrol-1-yl)-1-H-pyrazole-3-carboxamides. (hindawi.com)
  • Comparison of Cannabinoid CB 1 Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [ 18 F]MK-9470," International Journal of Molecular Imaging , vol. 2011, Article ID 548123, 11 pages, 2011. (hindawi.com)
  • The molecular mass of the protein estimated from Western blot analysis was 58 kDa, which is in concordance with previous data for CB1 in other tissues. (420magazine.com)
  • Results from this study provide better understanding of the molecular mechanisms of biased signaling at the CB1 receptor specifically, and in Class A GPCRs in general. (uncg.edu)
  • In the third chapter, molecular dynamics simulations are presented that were used to investigate the docking of 5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(2- methoxyethoxy)-3-pyridinecarboxamide (14h) inside the CB1 receptor. (uncg.edu)
  • Current studies increase our molecular level understanding of the conformational changes that accompany CB1 receptor activation. (uncg.edu)
  • The discovery of this receptor helped provide a molecular explanation for the established effects of cannabinoids on the immune system. (wikipedia.org)
  • Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer G?i? (grantome.com)
  • However although P2X7 receptor activation is well recognized to regulate processing and release of cytokines little is known concerning its role in regulating the Cladribine transcription of inflammatory genes nor the molecular mechanisms underlying these transcriptional effects. (technumber.com)
  • 1998) the molecular mechanisms underlying potential stimulatory or inhibitory transcriptional effects of P2X7 receptors on the expression of these or other inflammatory mediators have not been well characterized. (technumber.com)
  • [8] The discovery of this receptor helped provide a molecular explanation for the established effects of cannabinoids on the immune system. (wikipedia.org)
  • The molecular structure of CB1 (yellow ribbon) bound with AM6538 (orange stick structure). (nih.gov)
  • Detects a band of approximately 60 kDa (predicted molecular weight: 53 kDa).Can be blocked with Cannabinoid Receptor I peptide (ab50542) . (abcam.com)
  • Our findings provide biochemical evidence for sex- and hormone- dependent differences in the density and function of CB1 receptors in selected brain regions, and in behaviours associated with greater vulnerability to drug addiction, revealing a more vulnerable behavioural phenotype in female than in male rats. (eurekaselect.com)
  • Because a variety of neuroprotective genes are induced in cerebral ischemia, we examined the effect of experimental stroke, produced by 20 minutes of middle cerebral artery occlusion in rats, on CB1 receptor expression. (unthsc.edu)
  • Although cannabinoids have functional and morphologic effects in the prostate gland, the expression of cannabinoid receptors in this tissue has never been investigated. (420magazine.com)
  • The CB1 receptor was present in the ovarian surface epithelium (OSE), the granulosa cells of antral follicles, and the luteal cells of functional corpus luteum (CL). (docme.ru)
  • In the functional CL, the CB2 receptor was detected in the luteal cells. (docme.ru)
  • In vitro , CE-178253 exhibits sub-nanomolar potency at human CB 1 receptors in both binding (K i = 0.33 nM) and functional assays (K i = 0.07 nM). (biomedcentral.com)
  • These data are consistent with a revised model in which domain-specific endocytosis regulates the functional polarization of CB1 receptors, but this process is distinct from constitutive activity. (dundee.ac.uk)
  • Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. (strath.ac.uk)
  • However, most previous studies have looked only at the efferent functions of the bladder when studying the functional activity of cannabinoid receptors. (biomedcentral.com)
  • However, the compound exhibits higher affinity for the human CB1 receptor compared to rodent CB1. (uncg.edu)
  • Thus, results from the docking study will help in the remodeling of the CB1 receptor's N-terminus based on a mutational study that identified an N-terminal residue (M106 in rodent CB1 compared to I105 in human CB1) as the determinant of the species differential affinity of 14h at the CB1 receptor. (uncg.edu)
  • We submit every batch of receptor to stringent quality control testing that includes saturation radioligand binding assay to determine receptor concentration (Bmax) and affinity (Kd). (perkinelmer.com)
  • The corresponding amide analogues were compared to the hydrazides to determine the effect of the second nitrogen on receptor binding affinity. (elsevier.com)
  • In general, increasing the length and bulk of the substituent was associated with increased receptor affinity and efficacy (as measured in a guanosine 5'-triphosphate-gamma-[S-35] assay). (elsevier.com)
  • However, in most instances, receptor affinity and efficacy increases were no longer observed after a certain chain length was reached. (elsevier.com)
  • The in vitro binding affinity of Imidazole 24b for recombinant human and rat CB(1) receptor is 4 and 10 nM, respectively. (scienceexchange.com)
  • Recent studies have suggested that cell migratory responses are often mediated by G i protein-coupled receptors. (aspetjournals.org)
  • In addition, these data suggest that activation of mitogen-activated protein kinase plays an important role, whereas inhibition of adenylate cyclase is probably not involved in the cell migration mediated by CB1. (aspetjournals.org)
  • Activity within these circuits is modulated by a variety of G-protein-coupled receptors. (frontiersin.org)
  • Expression of mGluR2 metabotropic glutamate receptors, another pertussis toxin-sensitive G-protein-coupled receptor, had no effect on the signaling by NE or SOM. (jneurosci.org)
  • reported that SR 141716A inhibited the activation of mitogen-activated protein kinase by the pertussis toxin-sensitive tyrosine kinase receptors insulin and insulin-like growth factor in cells transfected with hCB1 receptors. (jneurosci.org)
  • These authors hypothesized that SR 141716A converts a tonically active hCB1 receptor into an active negative state in which the receptor is coupled to a GDP-bound G-protein. (jneurosci.org)
  • G-protein sequestration occurs because the population of CB1 cannabinoid receptors exists in both an inactive G-protein-precoupled RG GDP state and a constitutively active R*G GTP state. (jneurosci.org)
  • In addition, we tested the hypothesis that the conserved aspartate (D2.50) in the second transmembrane domain of the CB1 cannabinoid receptor is crucial for constitutive activity and G-protein sequestration. (jneurosci.org)
  • We hypothesized that the proximal C-terminal tail of the CB1 cannabinoid receptor is responsible for constitutive activity and that the distal C-terminal tail acts to prevent G-protein activation. (jneurosci.org)
  • Thus the CB1-D164N mutation may destabilize G-protein coupling. (jneurosci.org)
  • We therefore hypothesized that the aspartate in the second transmembrane domain of the CB1 receptor plays a crucial role in stabilizing the G-protein-coupled conformation of the receptor. (jneurosci.org)
  • To date, two types of cannabinoid receptors have been cloned in humans, namely CB1 and CB2 belonging to the G protein-coupled receptor superfamily. (420magazine.com)
  • The cannabinoid receptor expressed in the prostate negatively regulates adenylyl cyclase activity through a pertussis toxin-sensitive protein. (420magazine.com)
  • The present studies suggest D 2 receptors may have a significant modulatory role in determining the G protein coupling specificity of CB 1 receptors. (aspetjournals.org)
  • The present results demonstrate opposite changes in CB(1) and CB(2) receptor protein expression in human gliomas. (420magazine.com)
  • The G-protein-coupled central cannabinoid receptor (CB1) has been shown to be functionally associated with several biological responses including inhibition of adenylate cyclase, modulation of ion channels and induction of the immediate-early gene Krox-24. (biochemj.org)
  • This suggests that the signal transduction pathway between CB1 and MAP kinases involves a pertussis-toxin-sensitive GTP-binding protein and is independent of cyclic AMP metabolism. (biochemj.org)
  • These cannabinoids bind to 2 different cell surface G-protein-coupled receptors (GPCR), CB1 and CB2. (aacrjournals.org)
  • One possible mechanism is direct receptor-receptor interactions, as has been demonstrated for a number of G‐protein‐coupled receptors. (deepdyve.com)
  • 2 In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged μ, δ and κ opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. (deepdyve.com)
  • 4 In order to examine the implications of these interactions to signaling, we used GTPγS binding and mitogen‐activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. (deepdyve.com)
  • The CB1 receptor is a class A G-protein coupled receptor (GPCR), and is the most abundant neuro-modulatory receptor in the CNS. (uncg.edu)
  • 1997). One major signal transduction pathway for THC and the endocannabinoids is via the G-protein-coupled CB1 and CB2 receptors (Howlett and Mukhopadhyay, 2000). (docme.ru)
  • The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. (wikipedia.org)
  • The major goal of the proposed research is to demonstrate that the ligand can trigger to induce or stabilize receptor serial micro-conformational changes requisite to G-protein activation by using a protein MD simulations approach. (grantome.com)
  • In the present studies we identify that the transcription factors early growth response (Egr)-1 -2 and -3 are downstream signaling targets of P2X7 receptors in microglia and that their activation is sensitive to MEK and p38 mitogen-activated protein kinase (MAPK) inhibitors. (technumber.com)
  • However in this regard NFAT was very recently shown to mediate the transcriptional effects of P2X7 receptors on CC-chemokine ligand (CCL)3 (also called macrophage inflammatory protein (MIP) -1 alpha) expression in microglia (Kataoka et al. (technumber.com)
  • P2X7 receptors are well-known to promote the activation of the mitogen-activated protein (MAP) kinases ERK-1/-2 and p38 in both microglia and macrophages (reviewed in (Potucek et al. (technumber.com)
  • The cannabinoid receptor is a typical member of the largest known family of receptors called a G protein-coupled receptor . (wikipedia.org)
  • We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. (strath.ac.uk)
  • 12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. (strath.ac.uk)
  • Belongs to the G-protein coupled receptor 1 family. (abcam.com)
  • Cannabinoid receptor type 1 ( CB 1 ), also known as cannabinoid receptor 1 , is a G protein-coupled cannabinoid receptor that in humans is encoded by the CNR1 gene . (wikipedia.org)
  • The CB 1 receptor shares the structure characteristic of all G-protein-coupled receptors, possessing seven transmembrane domains connected by three extracellular and three intracellular loops, an extracellular N-terminal tail, and an intracellular C-terminal tail. (wikipedia.org)
  • [8] [9] The receptor may exist as a homodimer or form heterodimers or other GPCR oligomers with different classes of G-protein-coupled receptors . (wikipedia.org)
  • Upon activation, CB 1 receptor exhibits its effects mainly through activation of G i , which decreases intracellular cAMP concentration by inhibiting its production enzyme , adenylate cyclase , and increases mitogen-activated protein kinase (MAP kinase) concentration. (wikipedia.org)
  • This inhibition grows more pronounced when considered with the effect of activated CB 1 receptors to limit calcium entry into the cell, which does not occur through cAMP but by a direct G-protein-mediated inhibition. (wikipedia.org)
  • arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner. (grantome.com)
  • Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which regulates a number of cellular processes in mature and developing tissues. (wikipedia.org)
  • Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively activated macrophages. (bordeaux-neurocampus.fr)
  • Thus, modulation of CB1 regulates glucose uptake at the level of the PI3K signaling system in skeletal muscle cells. (unisa.it)
  • These data provide evidence for the active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA action during PD therapy. (scienceopen.com)
  • However, the dose-impact curves of EC exercise are in lots of situations biphasic, because sustained robust exercise results in EC receptor desensitization and down-regulation, resulting in progressive loss or even reversal of the impact. (randomeyes.net)
  • CB1 knockouts are also completely resistant to trabecular bone loss induced by ovariectomy, suggesting an important role for this receptor in hormonal regulation of bone loss. (sciencemag.org)
  • The immunohistochemical distribution and subcellular localization of the cannabinoid CB1 receptor was determined in the adult monkey using a polyclonal antiserum raised against the amino terminus of the rat CB1 receptor. (nih.gov)
  • Here, we have investigated the anatomical distribution of the CB1 receptor in the primate brain and characterized the cellular localization and synaptic targets of the CB1 receptor in the primate DLPFC. (pitt.edu)
  • We also characterized the expression of CB 1 receptors in the bladder and their localization and co-expression with TRPV1, a marker of nociceptive afferents. (biomedcentral.com)
  • Research over the last decade has shown that endocannabinoid/CB1 receptor signaling exerts powerful inhibitory effects on both glutamatergic and GABAergic synaptic transmission in the basal ganglia and many other brain regions. (frontiersin.org)
  • These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB 1 and GABA A receptors in control of food intake in neonatal layer chicks. (scielo.br)
  • Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. (ac.be)
  • Plasticity in interneurons with CP-AMPA receptors strongly modulates disynaptic GABAergic transmission onto CA1 pyramidal cells. (ox.ac.uk)
  • The present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative. (diva-portal.org)
  • To test this hypothesis, modified Boyden chamber assays were used to investigate cell migration mediated by CB1 cannabinoid receptors. (aspetjournals.org)
  • The high affinities of these pyrrole derivatives relative to JWH-030 (1,R = C5H11) support the hypothesis that these pyrroles interact with the CB, receptor primarily by aromatic stacking. (rti.org)
  • A set of hypothesis-driven mutations on the CB1 receptor yielded a CB1 receptor that exhibits biased signaling through the ß-arrestin pathway. (uncg.edu)
  • These results reinforce the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol. (uclouvain.be)
  • In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation. (thctotalhealthcare.com)
  • We demonstrate here that young mice (6-7 weeks) with a genetic deletion of the cannabinoid CB1 receptor performed as well as WT mice, or often better, in a number of learning and memory paradigms, including animal models of skill-learning, partner recognition, and operant conditioning. (pnas.org)
  • In contrast, the performance of mature mice (3-5 months) lacking CB1 receptors was much worse than that of age-matched WT animals. (pnas.org)
  • In most tests, these mice performed at the same level as old animals (14-17 months), suggesting that the decline in cognitive functions is accelerated in the absence of CB1 receptors. (pnas.org)
  • Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. (nih.gov)
  • To elucidate the behavioral effects of specific CB1 receptor deficiency, D1CB1-/- mice were submitted to a battery of behavioral tests which included exploration-based tests, depressive-like behavioral tests, and fear-related memory paradigms. (uni-muenchen.de)
  • Present at lower expression levels than CB 1 Rs, differences arising from different staining protocols and complications with negative controls, such as CB 2 R-KO mice have delayed confirmation of the presence of these receptors in the CNS (Munro et al. (springer.com)
  • Recently, knockout mice deficient in the CB1 cannabinoid receptor have been generated, and these animals result in an excellent tool to evaluate the neurophysiology of the endogenous cannabinoid system. (cannabis-marijuana.com)
  • OBJECTIVES: To establish the role of the CB1 cannabinoid receptor in several emotional-related behavioural responses, including aggressiveness, anxiety, depression and learning models, using CB1 knockout mice. (cannabis-marijuana.com)
  • METHODS: We evaluated the spontaneous responses of CB1 knockout mice and wild-type controls under different behavioural paradigms, including the light/dark box, the chronic unpredictable mild stress, the resident-intruder test and the active avoidance paradigm. (cannabis-marijuana.com)
  • RESULTS: Our findings showed that CB1 knockout mice presented an increase in the aggressive response measured in the resident-intruder test and an anxiogenic-like response in the light/dark box. (cannabis-marijuana.com)
  • Furthermore, a higher sensitivity to exhibit depressive-like responses in the chronic unpredictable mild stress procedure was observed in CB1 knockout mice, suggesting an increased susceptibility to develop an anhedonic state in these animals. (cannabis-marijuana.com)
  • Finally, CB1 knockout mice showed a significant increase in the conditioned responses produced in the active avoidance model, suggesting an improvement of learning and memory processes. (cannabis-marijuana.com)
  • Subsequently, it was shown that CB2 knock out mice, produced the same immunohistochemical staining, indicating the presence of the CB2 receptor where none was expressed. (wikipedia.org)
  • In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice. (bordeaux-neurocampus.fr)
  • Compared with controls, Ati-CB1-KO mice showed decreased body weight, reduced total adiposity, improved insulin sensitivity, enhanced energy expenditure, and fat depot-specific cellular remodeling toward lowered energy storage capacity and browning of white adipocytes. (bordeaux-neurocampus.fr)
  • Finally, the lean phenotype of Ati-CB1-KO mice and the increase in alternatively activated macrophages in adipose tissue were also present at thermoneutral conditions. (bordeaux-neurocampus.fr)
  • Administration had no effect in cannabinoid CB(1) receptor-deficient mice. (scienceexchange.com)
  • When the CB1 receptor is knocked out in mice, these animals are typically leaner and fewer hungry than wild-sort mice. (randomeyes.net)
  • When they exposed them to these signals, mice that were deficient in cannabinoid receptors in the habenula expressed neither the fear nor the repulsion observed in normal mice. (eurekalert.org)
  • CB1 knockout mice display increased bone mineral density as compared with normal littermates. (sciencemag.org)
  • see " The Plot Thickens on Thin Bones "), whereas cultured osteoclast cells derived from CB1 knockout mice are resistant to the effects of AM251. (sciencemag.org)
  • Studies of CB1 knockout mice have shown that CB1 is involved in the motivational properties of opiates and in the development of physical dependence on these drugs. (sciencemag.org)
  • Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. (sciencemag.org)
  • The aim of this study was to analyze the expression of cannabinoid receptors in the human prostate gland and their regulatory effects on adenylyl cyclase activity. (420magazine.com)
  • Two types of cannabinoid receptors, CB1 and CB2, responsible for the effects of THC were discovered and cloned in the early 1990s. (wikipedia.org)
  • 3 We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid-cannabinoid interactions are receptor specific. (deepdyve.com)
  • CB1 receptors, the bigger of the two, are extraordinarily abundant in the brain: 10 times more plentiful than μ- opioid receptors , the receptors responsible for the effects of morphine . (wikipedia.org)
  • activation of cannabinoid CB1 but not opioid receptors. (usdoj.gov)
  • GABA exerts its effect via two distinct receptors including the bicuculline-sensitive GABA A receptor and the bicuculline-insensitive GABA B receptors ( Stratford and Wirtshafter, 2013 ). (scielo.br)
  • We found that CB1 receptors are highly expressed in the primate DLPFC and that CB1 receptors are localized in the terminals of the subtype of perisomatic-targeting GABA interneurons that contain the neuropeptide cholecystokinin (CCK). (pitt.edu)
  • The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. (strath.ac.uk)
  • Persistent activation of D 2 receptors resulted in heterologous sensitization of adenylate cyclase to subsequent stimulation by forskolin, whereas the persistent activation of CB 1 receptors did not. (aspetjournals.org)
  • Moreover using RNAi we demonstrate that Egr factors and P2X7 receptors are necessary for BzATP-mediated attenuation of iNOS and stimulation of TNF-α and IL-6 gene expression. (technumber.com)
  • Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways. (thctotalhealthcare.com)
  • The principal endogenous ligand for the CB2 receptor is 2-Arachidonoylglycerol (2-AG). (wikipedia.org)
  • Based on computer modeling, ligand interactions with CB2 receptor residues S3.31 and F5.46 appears to determine differences between CB1 and CB2 receptor selectivity. (wikipedia.org)
  • Taken together, these results indicate a peripheral modulation by the cannabinoid system of bladder hypersensitivity during inflammation. (biomedcentral.com)
  • The cannabinoid CB 1 receptor transmembrane helix (TMH) 3−4−5−6 region includes an aromatic microdomain comprised of residues F3.25, F3.36, W4.64, Y5.39, W5.43, and W6.48. (kennesaw.edu)
  • Long term cannabinoid receptor (CB1) blockade in obesity : implications for the development of colorectal cancer. (lancs.ac.uk)
  • Blockade of CB1 receptor activity by genetic invalidation also decreases rewarding effects of opiates and alcohol in animals. (cannabis-marijuana.com)
  • Although CB1 receptor blockade is generally ineffective in reducing the self-administration of cocaine in rodents and primates, it reduces the reinstatement of extinguished cocaine-seeking behavior produced by cocaine-associated conditioned stimuli and cocaine priming injections. (cannabis-marijuana.com)
  • Similarly, CB1 receptor blockade is effective in reducing nicotine-seeking behavior induced by re-exposure to nicotine-associated stimuli. (cannabis-marijuana.com)
  • These findings indicate that CB1 receptors located in human vascular endothelium are functionally coupled to the MAP kinase cascade. (biochemj.org)
  • The expression of CB1 receptors on cultured porcine trabecular meshwork cells and the coupling of these receptors to p42/44 MAP kinase was determined by immunofluorescence microscopy and Western blot analysis. (arvojournals.org)
  • R ATIONALE: Endogenous and exogenous cannabinoids acting through the CB1 cannabinoid receptors are implicated in the control of a variety of behavioural and neuroendocrine functions, including emotional responses, and learning and memory processes. (cannabis-marijuana.com)
  • This system involves the type 1 cannabinoid receptors. (eurekalert.org)
  • Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. (frontiersin.org)
  • However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. (frontiersin.org)
  • While its distribution is similar to that in the rat, there are major differences, some of which may be significant when extrapolating the behavioral effects of cannabinoids observed in rodents to primates (e.g., humans). (nih.gov)
  • Effects of cannabinoid CB1 receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. (sigmaaldrich.com)
  • Cannabinoids exert a wide spectrum of effects in men including alterations in the reproductive system. (420magazine.com)
  • In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanisms of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation. (eurekaselect.com)
  • The effects of THC and endocannabinoids on many cell types appear to be mediated through the Gprotein-coupled CB1 and CB2 receptors. (docme.ru)
  • corpus luteum Although the mechanism of signal transduction by cannabinoids is only now being teased out, the effects of D9-tetrahydrocannabinol (THC) on female reproductive system have been known for decades. (docme.ru)
  • Future studies will investigate effects on identified inflammatory cells within the inflamed tissue to further elucidate the role of cannabinoid receptors. (ox.ac.uk)
  • These studies are the first to identify Egr factors as regulators of inflammatory gene expression following P2X7 receptor activation and suggest that P2X7 receptors may utilize the MAPK-Egr pathway to exert differential effects on microglial inflammatory activities which are beneficial to neuron survival. (technumber.com)
  • Because of the psychotropic effects of some cannabinoids, their clinical use is limited. (biomedcentral.com)
  • However, the effects of local activation of bladder cannabinoid receptors on afferent activity during inflammation are unknown. (biomedcentral.com)
  • Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. (cdc.gov)
  • This suggests that cannabinoids are playing an important role in nonopioid preconditioned placebo effects. (wired.com)
  • Scientists provided a detailed view of the primary molecule through which cannabinoids-the active compounds in marijuana-exert their effects on the brain. (nih.gov)
  • Cannabinoids exert their primary effects in the brain by binding the human cannabinoid (CB 1 ) receptor. (nih.gov)
  • These findings provide clues to the mechanisms by which different cannabinoids can exert somewhat differing effects. (nih.gov)
  • This complex structure will allow chemists to design diverse compounds that specifically target portions of the receptor to produce desired effects," says co-author Dr. Alexandros Makriyannis of Northeastern University. (nih.gov)
  • Involved in cannabinoid-induced CNS effects. (abcam.com)
  • Ameri, A. The effects of cannabinoids on the brain. (usdoj.gov)
  • Expression of hCB1 cannabinoid receptors abolished the Ca 2+ current inhibition by endogenous pertussis toxin-sensitive G i/o -coupled receptors for norepinephrine (NE) and somatostatin (SOM) but not by endogenous pertussis toxin-insensitive G s -coupled receptors for vasoactive intestinal polypeptide. (jneurosci.org)
  • The CB 1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. (wikipedia.org)
  • A synthetic cannabinoid inhibited CXCL12-induced migration and invasive properties of breast cancer cells. (greenmedinfo.com)
  • Durnett-Richardson J, Aanonsen L, Groves N, Jackson D, Hargreaves K (1995) Involvement of the spinal cannabinoid receptor in nociception. (springer.com)
  • These findings support the involvement of cannabinoid signaling in social alterations in psychiatry disorders. (uni-muenchen.de)
  • In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. (diva-portal.org)
  • One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. (diva-portal.org)
  • In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray. (diva-portal.org)
  • We also assessed changes in CB1 expression in the striatum during development. (frontiersin.org)
  • Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. (frontiersin.org)
  • At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. (frontiersin.org)
  • Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). (frontiersin.org)
  • The expression of cannabinoid receptors in the basal ganglia has important implications for motor dysfunction, such as Parkinson's disease (PD). (springer.com)
  • We observed expression of CB1 (24%) and CB2 (55%) in NSCLC patients. (aacrjournals.org)
  • Advances in crystallization and expression techniques made the crystallization of the CB1 receptor possible. (uncg.edu)
  • Epigenetic investigations revealed reduced levels of histone H3K9 acetylation (H3K9ac) associated to Npy and CB1 genes, which may represent a factor determining the dysregulation occurring at expression and signaling level. (diagenode.com)
  • Here we have scrutinized the expression profile of the CB1 receptor from the onset of neurogenesis in the chick embryo. (ox.ac.uk)
  • This has created a long history of debate as to the Central Nervous System expression of the CB2 receptor. (wikipedia.org)
  • This has the potential to resolve questions about the expression of CB2 receptors in various tissues. (wikipedia.org)
  • 2009) which is the first report to directly link these receptors to a transcription factor necessary for subsequent inflammatory gene expression in any cell type. (technumber.com)
  • Elevated CB2 receptor expression was identified in glioblastoma cells. (greenmedinfo.com)
  • During pathological conditions there is a change in the expression of cannabinoid receptors. (biomedcentral.com)
  • This study aimed to evaluate the immunohistochemical (IHC) expression of the cannabinoid receptor type-1 (CB1) and its association with CB1-1359G/A gene polymorphism (rs1049353) in the fallopian tubes in EP compared to controls. (cdc.gov)
  • These results demonstrate that the endogenous cannabinoid system in the habenula exclusively controls the expression of aversive memories, without influencing neutral or positive memories, and does so by selectively modulating acetylcholine in the neural circuits involved," explains Giovanni Marsicano, Inserm Research Director. (eurekalert.org)
  • Casellas, P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. (usdoj.gov)
  • CB1 receptor immunoreactivity (CB1IR) was rescored from previously published data using the same scale as pAkt-IR. (diva-portal.org)
  • Within the AD group, frontal cortical CB1 immunoreactivity correlated with cognitive scores assessed within a year of death. (ox.ac.uk)
  • The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca(2+) and the activation of specific 2-AG synthesizing (i.e. (sigmaaldrich.com)
  • In a natural way and independent of the marihuana, the cells themselves release compounds which are called endocannabinoids and they activate the CB1 and CB2 receptors to produce a physiological response. (innovations-report.com)
  • In addition, experimental studies have shown that cannabinoid CB1 receptors enhance liver fibrogenesis and steatogenesis by distinct mechanisms, therefore strongly supporting epidemiological findings. (medhelp.org)
  • A signature of this type of receptor is the distinct pattern of how the receptor molecule spans the cell membrane seven times. (wikipedia.org)
  • However, an emerging body of evidence suggests that the CB1 receptor may also play a role during development. (ox.ac.uk)
  • Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function. (ox.ac.uk)
  • Now, evidence has emerged that suggests an additional effect results from the cannabinoid pathway, according to a publication in Nature Medicine . (wired.com)
  • Some evidence suggests that cannabinoids might help to treat certain health conditions. (nih.gov)
  • CONCLUSIONS: Taken together these findings demonstrate that endogenous cannabinoids through the activation of CB1 receptors are implicated in the control of emotional behaviour and participate in the physiological processes of learning and memory. (cannabis-marijuana.com)
  • This causes an increase in the activity of the two neurotransmitters which are classified as endogenous cannabinoids. (wikipedia.org)
  • These results demonstrate that sensitization of bladder afferents induced by inflammation is partly suppressed by intravesical activation of cannabinoid receptors, an effect that appears to be mediated by CB 1 receptors. (biomedcentral.com)