A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
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.
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.
A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.
An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.
Drugs that bind to and activate dopamine receptors.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.
Purine bases found in body tissues and fluids and in some plants.
Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
The relationship between the dose of an administered drug and the response of the organism to the drug.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.
Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.
Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.
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.
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.
Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.
N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.
2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.
A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.
Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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 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.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.
A selective D1 dopamine receptor agonist used primarily as a research tool.
Drugs that bind to and activate adrenergic receptors.
A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.
Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A dopamine D2/D3 receptor agonist.
A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.
Drugs that bind to and activate excitatory amino acid receptors.
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.
A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
A family of hexahydropyridines.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
Drugs that selectively bind to and activate beta-adrenergic receptors.
Compounds with BENZENE fused to AZEPINES.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
Drugs that selectively bind to and activate alpha adrenergic receptors.
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 bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.
Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.
3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)
A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
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.
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.
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.
Drugs that bind to and activate cholinergic receptors.
Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.
The rate dynamics in chemical or physical systems.
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.
A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.
OXAZINES with a fused BENZENE ring.
Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
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.
Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT3 RECEPTORS.
Elements of limited time intervals, contributing to particular results or situations.
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)
The observable response an animal makes to any situation.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Compounds that bind to and activate PURINERGIC RECEPTORS.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.
Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
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.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.
A series of structurally-related alkaloids that contain the ergoline backbone structure.
One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.
A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.
Histamine substituted in any position with one or more methyl groups. Many of these are agonists for the H1, H2, or both histamine receptors.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.
Catalyze the hydrolysis of nucleosides with the elimination of ammonia.
Established cell cultures that have the potential to propagate indefinitely.
A subtype of G-protein-coupled SEROTONIN receptors that preferentially couple to GS STIMULATORY G-PROTEINS resulting in increased intracellular CYCLIC AMP. Several isoforms of the receptor exist due to ALTERNATIVE SPLICING of its mRNA.
A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.
Drugs used to cause dilation of the blood vessels.
Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.
A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.
Agents inhibiting the effect of narcotics on the central nervous system.
The physical activity of a human or an animal as a behavioral phenomenon.
Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.
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 serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION.
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.
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 ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.
Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.
A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.
Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.
Drugs that bind to and block the activation of PURINERGIC RECEPTORS.
A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.
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.
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)
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.
A highly potent and specific histamine H2 receptor agonist. It has been used diagnostically as a gastric secretion indicator.
A serotonin receptor subtype found primarily in the CENTRAL NERVOUS SYSTEM and the CHOROID PLEXUS. This receptor subtype is believed to mediate the anorectic action of SEROTONIN, while selective antagonists of the 5-HT2C receptor appear to induce ANXIETY. Several isoforms of this receptor subtype exist, due to adenine deaminase editing of the receptor mRNA.
The most common inhibitory neurotransmitter in the central nervous system.
Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.
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.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
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 class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)
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 dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.
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 voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.
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.
Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503)
5'-Adenylic acid, monoanhydride with sulfuric acid. The initial compound formed by the action of ATP sulfurylase on sulfate ions after sulfate uptake. Synonyms: adenosine sulfatophosphate; APS.
The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
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.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
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.
Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.
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.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.
Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.

Alteration of the purinergic modulation of enteric neurotransmission in the mouse ileum during chronic intestinal inflammation. (1/122)

1. The effect of chronic intestinal inflammation on the purinergic modulation of cholinergic neurotransmission was studied in the mouse ileum. Chronic intestinal inflammation was induced by infection of mice with the parasite Schistosoma mansoni during 16 weeks. 2. S. mansoni infection induced a chronic inflammatory response in the small intestine, which was characterised by intestinal granuloma formation, increased intestinal wall thickness, blunted mucosal villi and an enhanced activity of myeloperoxidase. 3. In control ileum and in chronically inflamed ileum, electrical field stimulation (EFS) of longitudinal muscle strips induced frequency-dependent contractions that were abolished by tetrodotoxin (TTX) and atropine. Carbachol induced dose-dependent contractions that were not affected by TTX but abolished by atropine. 4. In control ileum, adenosine and ATP dose-dependently inhibited the contractions to EFS. Theophylline and 8-phenyltheophylline, P(1) and A(1) receptor antagonists respectively, prevented this inhibitory effect of adenosine and ATP. PPADS, DMPX and MRS 1220, antagonists of P(2), A(2) and A(3) receptors, respectively, did not prevent this inhibitory effect of adenosine and ATP. Adenosine and ATP did not affect the contractions to carbachol. 5. The inhibitory effect of adenosine and ATP on contractions to EFS in control ileum was mimicked by the stable adenosine analogue methyladenosine and by the A(1)-receptor agonist N(6)-cyclohexyladenosine, but not by the A3 receptor agonist 2-Cl IB-MECA or by the ATP analogues alphabeta-methylene-ATP and ADPbetaS. The inhibitory effect of adenosine on contractions to EFS was lost after prolonged (90 min) treatment of control ileum with methyladenosine (100 micro M). 6. In chronically inflamed ileum, adenosine, methyladenosine, N(6)-cyclohexyladenosine and ATP all failed to inhibit the cholinergic nerve-mediated contractions to EFS. Also theophylline, 8-phenyltheophylline, PPADS, DMPX and MRS 1220 had no effect on the contractions to EFS and carbachol. The loss of effect of adenosine and ATP was still evident after 52 weeks of infection. 7. These results indicate that in physiological conditions neuronal adenosine A(1) receptors modulate cholinergic nerve activity in the mouse ileum. However, during chronic intestinal inflammation, this purinergic modulation of cholinergic nerve activity is impaired. This suggests that chronic intestinal inflammation leads to a dysfunction of specific neuronal regulatory mechanisms in the enteric nervous system.  (+info)

Comparison of effects of MgCl2 and Gpp(NH)p on antagonist and agonist radioligand binding to adenosine A1 receptors. (2/122)

AIM: To investigate modulation of antagonist and agonist binding to adenosine A1 receptors by MgCl2 and 5 -guanylimidodiphosphate (Gpp(NH)p) using rat brain membranes and the A1 antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the A1 agonist [3H]-2-chloro-N6-cyclopentyladenosine ([3H]CCPA). METHODS: Parallel saturation and inhibition studies were performed using well-characterised radioligand binding assays and a Brandel Cell Harvester. RESULTS: MgCl2 produced a concentration-dependent decrease (44%), whereas Gpp(NH)p increased [3H]DPCPX binding (19%). In [3H]DPCPX competition studies, agonist affinity was 1.5-14.6-fold higher and 4.6-10-fold lower in the presence of 10 mmol/L MgCl2 and 10 micromol/L Gpp(NH)p respectively; antagonist affinity was unaffected. The decrease in agonist affinity with increasing Gpp(NH)p concentrations was due to a reduction in the proportion of binding to the high affinity receptor state. In contrast to [3H]DPCPX, MgCl2 produced a concentration-dependent increase (72%) and Gpp(NH)p a decrease (85%) in [3H]CCPA binding. Using [3H]CCPA, agonist affinities were 5-17-fold higher than those for [3H]DPCPX, consistent with binding only to the high affinity receptor state. Agonist affinity was 1.3-10.5-fold higher and 2.4-4.7-fold lower on adding MgCl2 or Gpp(NH)p respectively; antagonist affinities were as for [3H]DPCPX. CONCLUSION: The inconsistencies surrounding the effects of MgCl2 and guanine nucleotides on radioligand binding to adenosine A1 receptors were systematically examined. The effects of MgCl2 and Gpp(NH)p on agonist binding to A1 receptors are consistent with their roles in stimulating GTP-hydrolysis at the G-protein alpha-subunit and in blocking formation of the high affinity agonist-receptor-G protein complex.  (+info)

Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. (3/122)

Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.  (+info)

Adenosine A1 receptor agonists block the neuropathological changes in rat retrosplenial cortex after administration of the NMDA receptor antagonist dizocilpine. (4/122)

Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) is known to induce neurotoxicity in rat retrosplenial cortex after systemic administration. The present study was undertaken to examine the effects of adenosine A(1) receptor agonists on the neurotoxicity in rat retrosplenial cortex after administration of dizocilpine. Pretreatment with adenosine A(1) receptor agonists, 2-chloro-N(6)-cyclopentyladenosine (CCPA) (0.1, 0.3, 1, or 3 mg/kg, intraperitoneally (i.p.)), or N(6)-cyclopentyladenosine (CPA) (1, 3, or 10 mg/kg, i.p.), attenuated neurotoxicity by dizocilpine (0.5 mg/kg, i.p), in a dose-dependent manner. Coadministration with adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 3 mg/kg, i.p.) significantly blocked the protective effects of CCPA for dizocilpine-induced neurotoxicity. Furthermore, pretreatment with CCPA (3 mg/kg) attenuated significantly the dizocilpine-induced expression of HSP-70 protein, which is known as a sensitive marker of reversible neuronal damage, and coadministration with DPCPX (3 mg/kg) blocked the inhibitory effects of CCPA for marked expression of HSP-70 protein by administration of dizocilpine. Moreover, pretreatment with CCPA (3 mg/kg, i.p.) significantly suppressed the increase of extracellular acetylcholine (ACh) levels in the retrosplenial cortex by administration of dizocilpine (0.5 mg/kg). In contrast, local perfusion of CCPA (1 microM) into the retrosplenial cortex via the dialysis probe did not alter the ACh levels by administration of dizocilpine (0.5 mg/kg), suggesting that the locus of action of CCPA is not in the retrosplenial cortex. These findings suggest that adenosine A(1) receptors agonists could protect against neuropathological changes in rat retrosplenial cortex after administration of the NMDA receptor antagonist dizocilpine.  (+info)

Allosteric enhancers of A1 adenosine receptors increase receptor-G protein coupling and counteract Guanine nucleotide effects on agonist binding. (5/122)

Endogenous ligands of G protein-coupled receptors bind to orthosteric sites that are topologically distinct from allosteric sites. Certain aminothiophenes such as (2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluromethyl)-phenyl]-methanone (PD81,723) and 2-amino-4,5,6,7-tetrahydro-benzo[b]thiophen-3-yl)-biphenyl-4-yl-methanone (ATL525) are positive allosteric regulators, or enhancers, of the human A1 adenosine receptor (A1AR). In equilibrium binding assays, 125I-N6-aminobenzyladenosine (125I-ABA) binds to two affinity states of A1AR with KD-high (0.33 microM) and KD-low ( approximately 10 nM). Enhancers have little effect on KD-high but convert all A1AR binding sites to the high-affinity state. Enhancers decrease the potency of guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) as an inhibitor of agonist binding by 100-fold and increase agonist-stimulated guanine nucleotide exchange. The association of 125I-ABA to high-affinity receptors on Chinese hamster ovary (CHO)-hA1 membranes does not follow theoretical single-site association kinetics but is approximated by a bi-exponential equation with t1/2 values of 1.85 and 12.8 min. Allosteric enhancers selectively increase the number of slow binding sites, possibly by stabilizing newly formed receptor-G protein complexes. A new rapid assay method scores enhancer activity on a scale from 0 to 100 based on their ability to prevent the rapid dissociation of 125I-ABA from A1AR in response to GTPgammaS. Compared with PD81,723, ATL525 (100 microM) scores higher (27 versus 79) and has less antagonist activity. ATL525 functionally enhances A1 signaling to inhibit cAMP accumulation in CHO-hA1 cells. These data suggest that simultaneously binding orthosteric and allosteric enhancer ligands convert the A1AR from partly to fully coupled to G proteins and prevents rapid uncoupling upon binding of GTPgammaS.  (+info)

Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced protection from cardiac ischemia. (6/122)

Activation of adenosine A1 or A3 receptors protects heart cells from ischemia-induced injury. The A3 receptor signals via RhoA and phospholipase D (PLD) to induce cardioprotection. The objective of the study was to investigate how RhoA activates PLD to achieve the anti-ischemic effect of adenosine A3 receptors. In an established cardiac myocyte model of preconditioning using the cultured chick embryo heart cells, overexpression of the RhoA-noninteracting PLD1 mutant I870R selectively blocked the A3 agonist (Cl-IBMECA, 10 nM)-induced cardioprotection. I870R caused a significantly higher percentage of cardiac cells killed in A3 agonist-treated than in A1 agonist (CCPA, 10 nM)-treated myocytes (ANOVA and posttest comparison, P<0.01). Consistent with its inhibitory effect on the PLD activity, I870R attenuated the Cl-IBMECA-mediated PLD activation. Cl-IBMECA caused a 41 +/- 15% increase in PLD activity in mock-transfected myocytes (P<0.01, paired t test) while having only a slight stimulatory effect on the PLD activity in I870R-transfected cells. To further test the anti-ischemic role of a direct RhoA-PLD1 interaction, atrial cardiac myocytes were rendered null for native adenosine receptors by treatment with irreversible A1 antagonist m-DITC-XAC and were selectively transfected with the human adenosine A1 or A3 receptor cDNA individually or they were cotransfected with cDNAs encoding either receptor plus I870R. I870R preferentially inhibited the human A3 receptor-mediated protection from ischemia. The RhoA-noninteracting PLD1 mutant caused a significantly higher percentage of cardiac cells killed in myocytes cotransfected with the human A3 receptor than in those cells expressing the human A1 receptor (ANOVA and posttest comparison, P<0.01). The present data provided the first demonstration of a novel physiological role for the direct RhoA-PLD1 interaction, that of potent protection from cardiac ischemia. The study further supported the concept that a divergent signaling mechanism mediates the anti-ischemic effect of adenosine A1 and A3 receptors.  (+info)

A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells. (7/122)

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.  (+info)

A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. (8/122)

The neuromodulator adenosine regulates immune activation and neuronal survival through specific G-protein-coupled receptors expressed on macrophages and neurons, including the A1 adenosine receptor (A1AR). Here we show that A1AR null (A1AR-/-) mice developed a severe progressive-relapsing form of experimental allergic encephalomyelitis (EAE) compared with their wild-type (A1AR+/+) littermates. Worsened demyelination, axonal injury, and enhanced activation of microglia/macrophages were observed in A1AR-/- animals. In addition, spinal cords from A1AR-/- mice demonstrated increased proinflammatory gene expression during EAE, whereas anti-inflammatory genes were suppressed compared with A1AR+/+ animals. Macrophages from A1AR-/- animals exhibited increased expression of the proinflammatory genes, interleukin-1beta, and matrix metalloproteinase-12 on immune activation when matched with A1AR+/+ control cells. A1AR-/- macrophage-derived soluble factors caused significant oligodendrocyte cytotoxicity compared with wild-type controls. The A1AR was downregulated in microglia in A1AR+/+ mice during EAE accompanied by neuroinflammation, which recapitulated findings in multiple sclerosis (MS) patients. Caffeine treatment augmented A1AR expression on microglia, with ensuing reduction of EAE severity, which was further enhanced by concomitant treatment with the A1AR agonist, adenosine amine congener. Thus, modulation of neuroinflammation by the A1AR represents a novel mechanism that provides new therapeutic opportunities for MS and other demyelinating diseases.  (+info)

TY - JOUR. T1 - Chronic caffeine exposure in rats blocks a subsequent nicotine-conditioned taste avoidance in a one-bottle, but not a two-bottle test. AU - Palmatier, Matthew I.. AU - Bevins, Rick A. PY - 2001/11/21. Y1 - 2001/11/21. N2 - Two experiments were conducted in order to investigate nicotine-conditioned taste avoidance (CTA) following chronic preexposure to caffeine. Rats were given daily intraperitoneal injections of caffeine anhydrous (0, 10, or 30 mg/kg) for 10 or 30 days. Training of the nicotine-CTA began after the last day of caffeine preexposure. On five separate occasions access to a saccharin solution was followed immediately by an injection of 1.2 mg/kg nicotine hydrogen tartrate salt or saline. Nicotine-CTA readily developed in saline-preexposed controls. That is, paired rats drank less saccharin solution than unpaired rats after repeated saccharin-nicotine pairings. A similar pattern of nicotine-CTA was found for rats preexposed to 30 mg/kg caffeine for 10 days. Following ...
204512-90-3 - OESBDSFYJMDRJY-BAYCTPFLSA-N - Tecadenoson [USAN:INN] - Similar structures search, synonyms, formulas, resource links, and other chemical information.
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No rebound inflammation after INO-1001 is discontinued. Rats were treated with INO-1001 (or vehicle) beginning 1 day after TBI in one of two regimens: i) for 12
This study was undertaken in order to investigate the effect of chronic treatment with 5′-chloro-5′-deoxy-(±)-ENBA, a potent and highly selective agonist of human adenosine A1 receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of the sciatic nerve. Chronic systemic administration of 5′-chloro-5′-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A1 adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. In addition, a single intraperitoneal injection of 5′-chloro-5′-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) 7 days post-SNI also reduced both symptoms for at least two hours. SNI was associated with spinal changes in microglial activation ipsilaterally to the nerve injury. Activated, hypertrophic microglia were significantly reduced by 5
Adenosine mediates its pysiological effects through four G protein-coupled receptors (A1, A2A, A2B and A3). A large number of agonists with high affinity at A1, A2A, A3 adenosine receptors and moderate affinity at A2B receptor have been developed over the years. Many compounds originally thought to be selective for the A1 or A2A subtypes later turned to be also potent agonists at more recently discovered A3 receptor. Owing to he great interest in A1 agonists as neuroprotective, antilipolytic, antiarrhythmic, and antinociceptive agents, there is a need for novel agonists with high potency and selectivity at this receptor subtype to avoid side effects due to the stimulation of the other subtypes. We discovered that the substitution of the hydrogen in 2-position of the ribose moiety of the A1 selective agonist CCPA with a methyl group (2-Me-CCPA) reduces the affinity at human A2A and A3 receptors, thus increasing the selectivity for A1 subtype [1]. In this communication we report on the affinity ...
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Buy Tianeptine online. Tianeptine is a new designer chemical, also called Coaxil. Tianeptine was found to be a μ-opioid receptor (MOR) full agonist using human proteins.Tianeptine is made on modern chemical equipment, professional chemists, which makes it as readable and of high quality.. Coaxil for sale online , Buy Tianeptine online. and all other synthetic opiates sold on this website are for research and legal applications. is a designer drug with obvious physiological and psychoactive effects.. ...
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TY - JOUR. T1 - Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl cyclase system in cerebellar granule cells. AU - Hettinger-Smith, Barbara D.. AU - Leid, Mark. AU - Murray, Thomas F.. PY - 1996/11. Y1 - 1996/11. N2 - Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3[3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for ...
The data presented in this study demonstrate that activation of PKC-ε on stimulation of the A1R in the rat or mouse heart elicits the translocation of the kinase to a RACK2 protein of the cardiomyocyte. Previously, we reported A1R activation promotes the translocation of PKC-ε, but not PKC-δ, to the t-tubules of the cardiomyocyte (30). The present data indicate that RACK2 was the target protein for this translocation. Our present observations include the measurement of contractile activity of isolated cardiomyocytes and the visualization with imaging (rat) and coimmunoprecipitation of the kinase and RACK2 (rat and mouse). Translocation of PKC-ε to RACK2 occurred whether the PKC-ε was activated nonspecifically by a phorbol ester, or by A1R activation with PIA, or with the selective agonist CCPA. The action induced by CCPA was selective for the A1R, as indicated by the inhibition elicited by the A1R antagonist DPCPX. Furthermore, PKC-ε translocation most likely results from an A1R-induced ...
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Slusarczyk J, Trojan E, Glombik K, et al. Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve Toll-like receptor-related pathways. J Neurochem. 2015 Dec 7. [Epub ahead of print]. PMID: 26640965.. Yoo I, Woo JM, Lee SH, et al. Influence of anxiety symptoms on improvement of neurocognitive functions in patients with major depressive disorder: A 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study. J Affect Disord. 2015 Oct 1;185:24-30. PMID: 26142691.. Lin H, Heo BH, Kim WM, et al. Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats. Neurosci Lett. 2015 Jun 26;598:91-5. PMID: 25982324.. Cooper CM, Whiting DA, Cowen PJ, et al. Tianeptine in an experimental medicine model of antidepressant action. J Psychopharmacol. 2015 May;29(5):582-90. PMID: 25759404. ...
TY - JOUR. T1 - Behavioral effects of nicotine, amphetamine and cocaine under a fixed- interval schedule of food reinforcement in rats chronically exposed to caffeine. AU - Jaszyna, Maria. AU - Gasior, Maciej. AU - Shoaib, Mohammed. AU - Yasar, Sevil. AU - Goldberg, Steven R.. N1 - Copyright: Copyright 2007 Elsevier B.V., All rights reserved.. PY - 1998. Y1 - 1998. N2 - Epidemiological surveys demonstrate that caffeine, the main psychoactive ingredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimulants, we examined the effects of chronic caffeine exposure on the behavioral responses to nicotine, amphetamine, cocaine, the selective D agonist SKF-82958 and the selective D2 receptor agonist NPA, in rats responding under a fixed interval (FI) schedule of food reinforcement. Following stabilization of rates and temporal patterns of responding (mathematically expressed as quarter-life values, QL), ...
Tianeptine is a drug used primarily in the treatment of major depressive disorder, although it may also be used to treat asthma or irritable bowel syndrome. Chemically it is a tricyclic antidepressant (TCA), but it has different pharmacological properties than typical TCAs as recent research suggests that tianeptine produces its antidepressant effects through indirect alteration of glutamate receptor activity (i.e., AMPA receptors and NMDA receptors) and release of BDNF, in turn affecting neural plasticity. Tianeptine was discovered and patented by The French Society of Medical Research in the 1960s. Currently, tianeptine is approved in France and manufactured and marketed by Laboratories Servier SA; it is also marketed in a number of other European countries under the trade name
This study is a 12-month, dose-level blinded, multicenter study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF episodes per day in PD patients experiencing motor fluctuations (OFF episodes). All patients will receive active treatment, but patients will be blinded to dose level. This will serve as an extension to the CVT-301-004 study for those patients who participated in that study and remain eligible for this study. In addition, patients who previously completed the CVT-301-003, CVT-301-009 and CVT-301-005 (observational arm completers), as well as CVT-301 naïve patients may be enrolled if they meet the CVT-301-004E eligibility criteria ...
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Adenosine A2A Receptor Agonist Polydeoxyribonucleotide Alleviates Interstitial Cystitis-Induced Voiding Dysfunction by Suppressing Inflammation and Apoptosis in Rats
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Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
We investigated the electrophysiological effects of cardiac hypertrophy induced by different experimental models. Comparison of the action potentials of hypertrophied and control rat hearts reveals a pronounced prolongation of the action potential fo
Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by MEDI0680 (AMP-514) may be included (eg, hearing loss) after consultation with the MedImmune medical ...
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... modified adenosine derivatives as high-affinity and selective agonists at the human A1 adenosine receptor with antinociceptive ... "N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists". Bioorganic & ... N6-Cyclopentyladenosine (CPA) is a drug which acts as a selective adenosine A1 receptor agonist. It has mainly cardiovascular ... Elzein E, Zablocki J (December 2008). "A1 adenosine receptor agonists and their potential therapeutic applications". Expert ...
"Repeated treatment with adenosine A1 receptor agonist and antagonist modifies the anticonvulsant properties of CPPene". ... is a drug which acts as a potent and selective antagonist for the adenosine A1 receptor. It has high selectivity for A1 over ... "Potent adenosine receptor antagonists that are selective for the A1 receptor subtype". Molecular Pharmacology. 31 (3): 247-52. ... It has been used to study the function of the adenosine A1 receptor in animals, which has been found to be involved in several ...
2-Chloro-N6-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor. It is similar to N6- ... a high affinity agonist radioligand for A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 340: 679-683. ...
... which has been shown to be an inverse agonist for adenosine A1 receptor sites. This action likely does not contribute to the ... Identification of isovaltrate as an inverse agonist at A1 receptors". Biochemical Pharmacology. 73 (2): 248-58. doi:10.1016/j. ... Valerenic acid in valerian stimulates serotonin receptors as a partial agonist, including 5-HT5A which is implicated in the ... Holzl J, Godau P (1989). "Receptor binding studies with Valeriana officinalis on the benzodiazepine receptor". Planta Medica. ...
... an adenosine A1 receptor agonist Cyclophosphamide Chiral phosphoric acid Cyclopropane fatty acid, a component of some rare fats ...
Adenosine modulates the preBötC output via activation of the A1 and A2A receptor subtypes. An adenosine A1 receptor agonist has ... Effects of adenosine A1 receptor activation". BMC Neuroscience. 9: 95. doi:10.1186/1471-2202-9-95. PMC 2567986. PMID 18826652. ... Another synthetic drug specific to the adenosine A2A receptor subtype is CGS-21680 that has been shown to cause apneas in 14- ... Since many of these neurons express GABA, glutamate, serotonin and adenosine receptors, chemicals custom tailored to bind at ...
Nakav S, Chaimovitz C, Sufaro Y (2008). Bozza P (ed.). "Anti-Inflammatory Preconditioning by Agonists of Adenosine A1 Receptor ... All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ... Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Extracellular ...
... an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist". Br J Pharmacol. 170 (6): 1167- ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ...
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors ... A1 receptors are paired with the G-proteins of Gi-1, Gi-2, Gi-3, Go1, and Go2. The g-proteins of A1 receptors continue to ... Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease ...
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... A1 receptors are also present in smooth muscle throughout the vascular system. The adenosine A1 receptor has been found to be ... "Adenosine Receptors: A1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels". ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ...
... with high selectivity over the other three adenosine receptor subtypes (ki values at human A1, A2A and A2B receptors are 4.1, ... structure-activity relationships and characterization of potent and selective inverse agonists at Human A3 adenosine receptors ... PSB-10 is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM ... Bilkei-Gorzo A, Abo-Salem OM, Hayallah AM, Michel K, Müller CE, Zimmer A (March 2008). "Adenosine receptor subtype-selective ...
... adenosine receptor antagonist, on the negative inotropic action of A(1) adenosine receptor full agonists in isolated guinea pig ... Dhalla AK, Shryock JC, Shreeniwas R, Belardinelli L (2003). "Pharmacology and therapeutic applications of A1 adenosine receptor ... The fraction of bound receptors is p. L. R. =. [. L. R. ]. [. R. ]. +. [. L. R. ]. =. 1. 1. +. K. d. [. L. ]. {\displaystyle {p ... receptor reserve is an integrative measure of the response-inducing capacity of an agonist (in some receptor models it is ...
... which triggers intracellular signal transduction via both adenosine A1 and A2 receptors[disambiguation needed], and that the ... Moreover, minoxidil contains a nitric oxide moiety and may act as a nitric oxide agonist. This may cause follicles in the ... expression of sulfonylurea receptor 2B in dermal papilla cells might play a role in the production of adenosine. Minoxidil ... Minoxidil is an adenosine 5'-triphosphate-sensitive potassium channel opener, causing hyperpolarization of cell membranes. ...
"The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". J. Biol. Chem ... 2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". J. Comp ... The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human ... alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting ...
... adenosine A1, AMPA, mGluR2/3, mGlu5, and OX2 receptors. In the rat cerebellum, the protein has also been found in the Golgi ... The 5-HT2A receptor is known primarily to couple to the Gαq signal transduction pathway. Upon receptor stimulation with agonist ... OSU-6162 acts as a partial agonist at both 5-HT2A and dopamine D2 receptors SN-22, partial agonist at all three 5-HT2 subtypes ... The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled ...
"The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia.". J. Biol. ... 2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system.". J. Comp ... alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting ... Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479-92. ...
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... This is a valuable guide to design potential 5HT1D receptor agonists. When sumatriptan binds there is major conformational ... 5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding ... Goadsby, P.J., Serotonin 5-HT1B/1D receptor agonists in migraine - Comparative pharmacology and its therapeutic implications. ...
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... 1999). "Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor". FASEB J. 12 (15): ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ...
The other three adenosine receptors are involved in bone formation. In Alzheimer's disease (AD), the expression of A1 and A2A ... Cerqueira, Manuel D (July 2004). "The future of pharmacologic stress: selective a2a adenosine receptor agonists". The American ... In the airways of patients with asthma, the expression of adenosine receptors is upregulated. Adenosine receptors affect ... the expression of adenosine receptors on the neutrophil, and the affinity of these receptors for adenosine. Micromolar ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... highly potent 5-HT1D receptor agonist.". Journal of medicinal chemistry 42 (3): 526-31. PMID 9986723. doi:10.1021/jm9805945. ... 5-HT1D receptor (5-hidroksitriptaminski (serotoninski) receptor 1D, HTR1D) je 5-HT receptor. On je kodiran istoimenim genom.[1] ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • ...
ATP targets P2X receptors, P2Y, and A1 receptors. ATP has several functions as a gliotransmitter, including insertion of AMPA ... Other less common gliotransmitters include: homocysteic acid, an endogenous N-methyl-(D)-aspartic acid receptor (NMDAR) agonist ... activity is controlled in the retina by the molecule's ability to hyperpolarize the neuron by converting from ATP to adenosine ... Its main target receptors include Kainate receptors, metabotropic glutamate receptors (mGluRs), and especially N-methyl D- ...
... histamine H3 receptor, μ opioid receptor, NMDA receptor, and adenosine A1 receptor. D1-D2 receptor complex D1−H3−NMDAR receptor ... All of these drugs are preferentially D2-like receptor agonists. Fenoldopam is a selective D1 receptor partial agonist that ... a target to prevent neurodegeneration D1-D3 receptor complex D1-NMDAR receptor complex D1-A1 receptor complex Dopamine receptor ... The D1 receptor forms heteromers with the following receptors: dopamine D2 receptor, dopamine D3 receptor, ...
... consist of Isoreceptors D1-D2 D1-D3 D2-D3 D2-D4 D2-D5 Non-isoreceptors D1-adenosine A1 D2-adenosine A2A D2-ghrelin receptor ... unless blocked by a receptor antagonist or a synthetic partial agonist. D3 is encoded by the Dopamine receptor D3 gene (DRD3). ... "Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes". Rev Neurosci. 27 (1 ... The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are ...
... specifically the A1-D1 receptor heterodimer (this is a receptor complex with 1 adenosine A1 receptor and 1 dopamine D1 receptor ... "Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer ... a receptor complex composed of 1 adenosine A1 receptor and 1 adenosine A2A receptor) in the axon terminal of glutamate neurons ... this is a receptor complex with 2 adenosine A2A receptors and 2 dopamine D2 receptors). The A2A-D2 receptor heterotetramer has ...
Structure of the adenosine A1 receptor reveals the basis for subtype selectivity. Cell 168: 867-877. Bradley, S.J., Bourgognon ... Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. Proc. ... Structure of the adenosine-bound human A1 receptor-Gi complex. Nature 558: 559-563. Harvey Motulsky, Arthur Christopoulos. ... Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature 555: 121-125. Liang, Y.L., ...
It is believed it acts as an adenosine A2A receptor neutral antagonist or as an inverse agonist. Caffeine's A2A receptor ... Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain. Frontiers in Bioscience. Volume 13. Pages 2391- ... Adenosine A2A receptor antagonists are a class of drugs that blocks adenosine at the adenosine A2A receptor. Notable adenosine ... adenosine receptor antagonists as potential therapeutics, antagonist for A2A-receptors, adenosine receptor ligands as anti- ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... 1999). „Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor.". FASEB J. 12 (15): ... Gao ZG, Jacobson KA (2007). „Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs. 12 (3): 479-92. PMID ... Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... Sullivan GW (November 2003). "Adenosine A2A receptor agonists as anti-inflammatory agents". Current Opinion in Investigational ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): ... "Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor ...
腺苷酸(英语:Adenosine receptor) (A1, A2A, A2B, A3) · P2Y(英语:P2Y receptor) (1(英语:P2RY1), 2(英语:P2RY2), 4(英语:P2RY4), 5(英语:LPAR6), 6(英语: ... SL65.0155(英语:SL65.0155) - partial agonist. *CJ-033,466(英语:CJ-033,466) - partial agonist ... 乙酰胆碱 (M1, M2, M3, M4, M5) · 多巴胺(英语:Dopamine receptor) (D1, D2, D3, D4, D5) · 组织胺(英语:Histamine receptor) (H1, H2, H3, H4) · 褪黑素( ... α1(英语:Alpha-1 adrenergic receptor) (A, B, D) · α2(英语:Alpha-2 adrenergic receptor) (A, B, C) · β1 · β2
... a selective agonist for PGE2 receptor subtype 3". Journal of Leukocyte Biology. 68 (2): 187-93. PMID 10947062.. ... "Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... 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 ...
D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... 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 ...
... discovery of a subtype selective agonist". Mol. Pharmacol. 58 (6): 1601-8. PMID 11093801.. ... 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# ...
mineralocorticoid receptor activity. • steroid binding. • G-protein coupled receptor activity. • steroid hormone receptor ... The development of the GPER-selective agonist G-114 has facilitated studies that demonstrate GPER activation induces acute ... 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 ...
Agonists[edit]. *Neurokinin B - endogenous peptide ligand, also interacts with other neurokinin receptors but has highest ... "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 ...
Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN- ... 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 ...
Receptor. (ligands). DP (D2). DP1. *Agonists: Prostaglandin D2. *Treprostinil ... 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) ...
It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.[28] For the signal to be ... Ephrins (A1, A2, A3, A4, A5, B1, B2, B3). *Erythropoietin (see here instead) ... Agonists: des(1-3)IGF-1. *Insulin-like growth factor-1 (somatomedin C) ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ...
"Structure of an agonist-bound human A2A adenosine receptor". Science. 332 (6027): 322-7. doi:10.1126/science.1202793. PMC ... The very large rhodopsin A group has been further subdivided into 19 subgroups (A1-A19).[11] ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors ( ... "The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor". Nature. 469 (7329): 241-4. doi: ...
GABAB receptor ligands.[citation needed] *Agonists: baclofen, propofol, GHB,[75] phenibut. ... Receptor/signaling modulators GABA receptor modulators GABAA receptor positive modulators Glutamate metabolism/transport ... Receptor/signaling modulators GABAA receptor positive modulators GABA metabolism/transport modulators ... Two general classes of GABA receptor are known:[4] *GABAA in which the receptor is part of a ligand-gated ion channel complex[5 ...
Ro10-5824 - partial agonist. *Roxindole - D4 selective but also D2 and D3 autoreceptor agonist, 5HT1A receptor agonist, ... The dopamine receptor D4 is a G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.[5] ... Inverse agonists[edit]. *FAUC F41: inverse agonist, subtype selectivity of more than 3 orders of magnitude over D2 and D3[42][ ... dopamine neurotransmitter receptor activity. • G-protein coupled receptor activity. • protein binding. • dopamine binding. • ...
However, β2 adrenergic receptor agonists are not recommended to treat ARDS because it may reduce survival rates and precipitate ... and low production of adenosine triphosphate (ATP), can cause myocardial depression, reducing cardiac contractility and causing ... the toll-like receptors, the C-type lectin receptors, the NOD-like receptors, and the RIG-I-like receptors. Invariably, the ... This forced receptor interaction induces the production of pro-inflammatory chemical signals (cytokines) by T-cells.[35] ...
... is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and ... with the C5a receptor, Formyl peptide receptor 1, and Formyl peptide receptor 2 receptors. DP2 has little or no such amino acid ... prostaglandin D receptor activity. • G-protein coupled receptor activity. • prostaglandin J receptor activity. • prostaglandin ... "Prostanoid Receptors: DP2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
15 A1,15 1.84 cM. Start. 3,317,760 bp[2]. End. 3,583,492 bp[2]. ... Ulimorelin; Non-peptide: Adenosine. *Anamorelin. *Capromorelin ... Binding of growth hormone to the receptor leads to receptor dimerization (the receptor may however also exist as a pre- ... receptor complex. • integral component of plasma membrane. • extracellular region. • cell surface. • growth hormone receptor ... 2aew: A model for growth hormone receptor activation based on subunit rotation within a receptor dimer ...
nonselective adenosine receptor antagonist,[23] antagonizing A1, A2, and A3 receptors almost equally, which explains many of ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth muscles and relaxes the ...
"Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: a possible sleep- ... D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... cannabinoid receptor 1 and CB1-OX1 receptor heterodimers,[40][41][42] adenosine A1 receptors,[43] muscarinic M3 receptors,[44] ... CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. ... In conclusion, orexin receptors ...
D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... receptor promoter: regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway". Endocrinology. 145 (12): ... "Corticotropin-releasing Factor Receptors: CRF2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic ... corticotrophin-releasing factor receptor activity. • transmembrane signaling receptor activity. • peptide hormone binding. • ...
D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... "Neurotensin Receptors: NTS1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Neurotensin receptor 1, also called NTR1, belongs to the large superfamily of G-protein coupled receptors and is considered a ... NTSR1, NTR, Neurotensin receptor 1, neurotensin receptor 1 (high affinity). External IDs. MGI: 97386 HomoloGene: 68261 ...
"C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained agonist-induced signaling. Role of receptor ... tachykinin receptor activity. • G-protein coupled receptor activity. • substance K receptor activity. • signal transducer ... "Tachykinin Receptors: NK2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Agonists[edit]. *GR-64349 - potent and selective agonist, EC50 3.7nM, 7-amino acid polypeptide chain. CAS# 137593-52-3 ...
This is called constitutive activity, and it means that the receptor is always "on," unless acted on by an inverse agonist. ... dopamine receptor type 2 (DRD2),[11] melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT2c receptor).[11] See ... Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth ... "Ghrelin Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.. ...
"Melanocortin 1 receptor agonists reduce proteinuria". Journal of the American Society of Nephrology. 21 (8): 1290-8. doi: ... melanin-activating peptide receptor, or melanotropin receptor, is a G protein-coupled receptor that binds to a class of ... "Melanocortin Receptors: MC1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... G protein-coupled receptor activity. • signal transducer activity. • melanocyte-stimulating hormone receptor activity. • GO: ...
See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Nicotinic acetylcholine receptor ... Latrophilins are a group of highly conserved G-protein coupled receptors from the adhesion G protein-coupled receptor family. ... These receptors were originally identified based on their ability to bind the spider venom alpha-latrotoxin.[1] This conserved ... "The latrophilins, "split-personality" receptors". Advances in Experimental Medicine and Biology. 706: 59-75. doi:10.1007/978-1 ...
Acute infusion of the drug LY354740 (also known as eglumegad, an agonist of the metabotropic glutamate receptors 2 and 3) ... Adenosine monophosphate. *Kainic acid. *Monosodium glutamate. References[edit]. *^ "L-Glutamic acid CAS#: 56-86-0". www. ... See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators ... glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated. Because of its role in ...
MilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA 25mg Life Sciences:Protein Biology:Protein Extraction and ... MilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA A potent and selective agonist of adenosine A1 receptor (A1R) (K ... A potent and selective agonist of adenosine A1 receptor (A1R) (Ki = 2.3 nM, 790 nM, 18.6µM, 43nM for human A1, A2A, A2B, and A3 ...
N6-substituted adenosines are full agonists at A1R and activate this receptor selectively over the other adenosine receptor ... Novel Irreversible Agonists Acting at the A1 Adenosine Receptor, Journal of Medicinal Chemistry, 2016, 59, 24, 11182. CrossRef ... and Biological Evaluation of Adenosines with Heterobicyclic and Polycyclic N6-Substituents as Adenosine A1 Receptor Agonists. ... The adenosine A1 receptor (A1R) affinity and potency of these compounds was initially assessed using competitive binding assays ...
Use of 11C-MPDX and PET to study adenosine A1 receptor occupancy by nonradioactive agonists and antagonists. Paul, S., Khanapur ... adenosine, adenosine A1 receptor, N-6-cyclopentyladenosine, caffeine, brain, positron emission tomography, PET ... BACKGROUND: Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8- ... PET imaging of adenosine A(1) receptor occupancy. Paul, S., Khanapur, S., Elsinga, P. H., Ishiwata, K., Meerlo, P., Dierckx, R. ...
Optimization of thermolytic response to A1 adenosine receptor agonists in rats Message Subject (Your Name) has forwarded a page ... Optimization of thermolytic response to A1 adenosine receptor agonists in rats. Isaac R Bailey, Bernard Laughlin, Lucille Moore ... Optimization of thermolytic response to A1 adenosine receptor agonists in rats. Isaac R Bailey, Bernard Laughlin, Lucille Moore ... Optimization of thermolytic response to A1 adenosine receptor agonists in rats. Isaac R Bailey, Bernard Laughlin, Lucille Moore ...
Our data suggest a possible use of adenosine A1 receptor agonist in neuropathic pain symptoms. ... a potent and highly selective agonist of human adenosine A1 receptor, on thermal hyperalgesia and mechanical allodynia in a ... Our results demonstrated an involvement of adenosine A1 receptor in the amplified nociceptive thresholds and in spinal glial ... a selective A1 adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial ...
8-Alkylamino-Substituted Analogs of N6-Cyclopentyladenosine Are Partial Agonists for the Cardiovascular Adenosine A1 Receptors ... Partial adenosine A1 receptor agonists with reduced intrinsic activity at the cardiovascular system would be promising for ... 8-Alkylamino-Substituted Analogs of N6-Cyclopentyladenosine Are Partial Agonists for the Cardiovascular Adenosine A1 Receptors ... 8-Alkylamino-Substituted Analogs of N6-Cyclopentyladenosine Are Partial Agonists for the Cardiovascular Adenosine A1 Receptors ...
... adenosine A1 receptors expressed on Chinese hamster ovary (CHO) cells, and to rat brain adenosine A1 receptors was undertaken. ... Thermodynamics of full agonist, partial agonist, and antagonist binding to wild-type and mutant adenosine A1 receptors. ... Thermodynamics of full agonist, partial agonist, and antagonist binding to wild-type and mutant adenosine A1 receptors ... Thermodynamics of full agonist, partial agonist, and antagonist binding to wild-type and mutant adenosine A1 receptors ...
Keywords:A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR ... Keywords: A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 ... A1 adenosine receptor agonists, antagonists, and allosteric modulators. In: ed, The Adenosine Receptors Springer. 2018; pp. 59- ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ...
Interactions of purified bovine brain A1-adenosine receptors with G-proteins. Reciprocal modulation of agonist and antagonist ... The bovine brain A1-adenosine receptor was purified 8000-fold by affinity chromatography on xanthine-amine-congener (XAC)- ... Interactions of purified bovine brain A1-adenosine receptors with G-proteins. Reciprocal modulation of agonist and antagonist ... Interactions of purified bovine brain A1-adenosine receptors with G-proteins. Reciprocal modulation of agonist and antagonist ...
Persistent Activation by and Receptor Reserve for an Irreversible A1-Adenosine Receptor Agonist in DDT1 MF-2 Cells and in ... Persistent Activation by and Receptor Reserve for an Irreversible A1-Adenosine Receptor Agonist in DDT1 MF-2 Cells and in ... Persistent Activation by and Receptor Reserve for an Irreversible A1-Adenosine Receptor Agonist in DDT1 MF-2 Cells and in ... Persistent Activation by and Receptor Reserve for an Irreversible A1-Adenosine Receptor Agonist in DDT1 MF-2 Cells and in ...
Adenosine A1 Receptor Agonist I, CPA - CAS 41552-82-3 - Calbiochem CAS 41552-82-3 - Find MSDS or SDS, a COA, data sheets and ... Adenosine A1 Receptor Agonist I, CPA - CAS 41552-82-3 - Calbiochem. 119135 Sigma-AldrichAdenosine A1 Receptor Agonist I, CPA - ... A potent and selective agonist of adenosine A1 receptor (A1R) (Ki = 2.3 nM, 790 nM, 18.6 µM, 43nM for human A1, A2A, A2B, and ... A potent and selective agonist of adenosine A1 receptor (A1R) (Ki = 2.3 nM, 790 nM, 18.6 µM, 43nM for human A1, A2A, A2B, and ...
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ... Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
title = "Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased ... T1 - Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ...
... is a selective A1 adenosine receptor agonist, can ameliorate noise- and Cisplatin-induced cochlear injury. Adenosine amine ... Adenosine amine congenerADACAdenosine ReceptorP1 receptorCochlearinjuryA1-adenosinehearinglosssystemicneuroprotective ... Adenosine amine congener (ADAC) is a selective A1 adenosine receptor agonist, can ameliorate noise- and Cisplatin-induced ... Adenosine amine congener (ADAC) is a selective A1 adenosine receptor agonist, can ameliorate noise- and Cisplatin-induced ...
The effect of GR79236, a highly selective adenosine A1 receptor agonist, on the treatment of neuropathic pain in the rat ... The effect of GR79236, a highly selective adenosine A1 receptor agonist, on the treatment of neuropathic pain in the rat ...
Tecadenoson: A Novel, Selective A1 Adenosine Receptor Agonist. Peterman, Carla; Sanoski, Cynthia A. ... Varenicline: A Selective α4β2 Nicotinic Acetylcholine Receptor Partial Agonist Approved for Smoking Cessation. Lam, Sum; Patel ... Vorapaxar: A Protease-Activated Receptor Antagonist for the Prevention of Thrombotic Events. Lam, Sum; Tran, Tran ... Vorapaxar: A Protease-Activated Receptor Antagonist for the Prevention of Thrombotic Events ...
Orally active a1 adenosine receptor agonists. US20020110593. Jun 4, 1999. Aug 15, 2002. Adel Penhasi. Delayed total release two ... Prodrugs for oxadiazole muscarinic agonists. US5273760. Dec 24, 1991. Dec 28, 1993. Euroceltigue, S.A.. Stabilized controlled ...
T1 - Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ... title = "Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor- ... Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ... Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ...
... thioxa and azacycloalkyl substituted adenosine derivative and a method for using the composition as an A1 adenosine receptor ... Justia Patents Adenosine Or DerivativeUS Patent Application for ORALLY ACTIVE A1 ADENOSINE RECEPTOR AGONISTS Patent Application ... and azacycloalkyl substituted adenosine derivative and a method for using the composition as an A1 adenosine receptor agonist. ... A1 and A2. Each subtype effects different physiological functions. Stimulation of the A1 adenosine receptor induces two ...
We assessed the role of the adenosine A1 receptor using the selective agonist CCPA. As shown in FIG. 1, CCPA induced autophagy ... The adenosine A1 receptor is a G-protein-coupled receptor that activates phospholipase C (PLC)24. To determine if PLC signaling ... Autophagy is Required for Preconditioning By the Adenosine A1 Receptor-Selective Agonist CCPA. The following example describes ... Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA. Basic Res Cardiol 104:157-167, ...
Dual acting antioxidant A1 adenosine receptor agonists.. Gregg A, Bottle SE, Devine SM, Figler H, Linden J, White P, Pouton CW ... 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 adenosine receptor agonist allosteric enhancers having improved potency. ... Allosteric enhancers of A1 adenosine receptors increase receptor-G protein coupling and counteract Guanine nucleotide effects ... Synthesis and evaluation of new N6-substituted adenosine-5-N-methylcarboxamides as A3 adenosine receptor agonists. ...
adenosine A1 receptor agonist An agonist at the A. 1. receptor.. Application(s):. nutraceutical A product in capsule, tablet or ... adenosine 5-monophosphate (CHEBI:16027) has role adenosine A1 receptor agonist (CHEBI:65057) adenosine 5-monophosphate (CHEBI ... adenosine 5-monophosphate (CHEBI:16027) is a adenosine 5-phosphate (CHEBI:37096) adenosine 5-monophosphate (CHEBI:16027) is ... adenosine 5-monophosphate(1+) (CHEBI:40721) is conjugate acid of adenosine 5-monophosphate (CHEBI:16027). adenosine 5- ...
Lee, Y. M., Sheu, J. R., & Yen, M. H. (1995). BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial ... BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion injury in rats. / Lee, Yen Mei; ... Lee, YM, Sheu, JR & Yen, MH 1995, BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion ... Fingerprint Dive into the research topics of BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial ...
The effect of GR190178, a selective low-efficacy adenosine A1 receptor agonist, on the treatment of neuropathic hyperalgesia in ... The effect of GR190178, a selective low-efficacy adenosine A1 receptor agonist, on the treatment of neuropathic hyperalgesia in ...
1991) Activity of N6-substituted 2-chloroadenosines at A1 and A2 adenosine receptors. J Med Chem 34(12):3388-3390. ... 2007) New fluorescent adenosine A1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains ... 2010) A novel highly selective adenosine A1 receptor agonist VCP28 reduces ischemia injury in a cardiac cell line and ischemia- ... 2012) The role of the second and third extracellular loops of the adenosine A1 receptor in activation and allosteric modulation ...
... with the human adenosine A1 receptor was investigated in the present study. Radioligand binding experiments were performed in ... the absence and presence of diverse allosteric modulators on both wild-type (wt) and mutant (T277A) adenosine A1 receptors … ... a full agonist, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an inverse agonist/antagonist, for the adenosine A1 receptor. ... This study indicates that the nonribose ligand, LUF5831, is a partial agonist for the adenosine A1 receptor. ...
A few years ago, adenosine deaminase was reported to appear on the surface of cells. Recently, it has been demonstrated that ... Adenosine deaminase is an enzyme of purine metabolism that has largely been considered to be cytosolic. ... adenosine deaminase interacts with a type II membrane protein known as … ... Purinergic P1 Receptor Agonists * Purinergic P1 Receptor Antagonists * Receptors, Purinergic P1 / metabolism* ...
Structure-kinetics relationships of Capadenoson derivatives as adenosine A1 receptor agonists.. Louvel J, Guo D, Soethoudt M, ... Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A3 Receptor. ... A covalent antagonist for the human adenosine A2A receptor.. Yang X, Dong G, Michiels TJM, Lenselink EB, Heitman L, Louvel J, ... Sodium ion binding pocket mutations and adenosine A2A receptor function.. Massink A, Gutiérrez-de-Terán H, Lenselink EB, Ortiz ...
Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A1 Receptor Antagonists (3) • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. MeSH ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ...
... an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist". Br J Pharmacol. 170 (6): 1167- ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ...
  • Here we investigated whether A1R occupancy by nonradioactive agonists and antagonists can be assessed with this technique. (rug.nl)
  • Agonists and antagonists may bind to different sites on the A1R protein having allosteric interactions. (rug.nl)
  • This review provides an overview of the medicinal chemistry and therapeutic potential of various agonists/partial agonists, antagonists and allosteric modulators of A1 AR, with a particular emphasis on their current status and future perspectives in clinical settings. (eurekaselect.com)
  • A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR. (eurekaselect.com)
  • A1 adenosine receptor agonists, antagonists, and allosteric modulators. (eurekaselect.com)
  • Primary cultures of cerebellar granule cells were exposed chronically to A 1 adenosine receptor agonists and antagonists. (elsevier.com)
  • The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A 1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. (elsevier.com)
  • Hettinger-Smith, BD, Leid, M & Murray, TF 1996, ' Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A 1 adenosine receptor-adenylyl cyclase system in cerebellar granule cells ', Journal of Neurochemistry , vol. 67, no. 5, pp. 1921-1930. (elsevier.com)
  • 3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists. (nih.gov)
  • 2-aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists. (nih.gov)
  • Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5. (nih.gov)
  • Structure-Affinity Relationships and Structure-Kinetic Relationships of 1,2-Diarylimidazol-4-carboxamide Derivatives as Human Cannabinoid 1 Receptor Antagonists. (nih.gov)
  • Kinetics of human cannabinoid 1 (CB1) receptor antagonists: Structure-kinetics relationships (SKR) and implications for insurmountable antagonism. (nih.gov)
  • The adenosine receptors are commonly known for their antagonists caffeine and theophylline , whose action on the receptors produces the stimulating effects of coffee , tea and chocolate . (wikipedia.org)
  • Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A 1 and A 2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. (wikipedia.org)
  • Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. (wikipedia.org)
  • Specific A 1 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3- dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine ( CCPA ). (wikipedia.org)
  • Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects. (wikipedia.org)
  • This is being contended and it is now considered a relative contraindication (however, selective adenosine antagonists are being investigated for use in treatment of asthma) Adenosine is an endogenous purine nucleoside that modulates many physiological processes. (wikipedia.org)
  • Adenosine receptors: development of selective agonists and antagonists. (biomedsearch.com)
  • Rather, adenosine-induced depotentiation is inhibited by specific antagonists of p38 MAPK, but not by a structural analog that does not inhibit p38. (jneurosci.org)
  • The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. (patents.com)
  • Carprolactams as Potent CGRP Receptor Antagonists for the Treament of Migraine", Bioorg Med. (patents.com)
  • Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice. (semanticscholar.org)
  • Described are uses of A.sub.2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses. (patents.com)
  • A.sub.2a receptor antagonists in particular are provided to enhance immune responses by reducing T-cell mediated tolerance to antigenic stimuli and agonists are provided to enhance effectiveness of immunosuppressive agents. (patents.com)
  • 0004] This application relates to uses of A.sub.2a adenosine receptor agonists and antagonists to modulate T-cell mediated tolerance to antigenic stimuli. (patents.com)
  • Several synthetic compounds have been shown to act on neurons specific to the preBötC, most being selective agonists or antagonists to receptor subtypes on neurons in the vicinity. (wikipedia.org)
  • Update on novel purinergic P2X3 and P2X2/3 receptor antagonists and their potential therapeutic applications. (wikipathways.org)
  • Potent adenosine receptor antagonists that are selective for the A1 receptor subtype. (wikipathways.org)
  • However, precise study of the function of these receptors has been hampered by lack of highly specific, potent, and selective A 1 AdoR antagonists. (asnjournals.org)
  • The concepts describing ligand interactions with receptors have also been refined from the simple binary concept of competitive agonists and antagonists to partial agonists, allosteric modulators and inverse agonists. (currentprotocols.com)
  • Our overall goals are to design, chemically synthesize, and characterize pharmacologically new agonists and antagonists for the four subtypes of adenosine receptors (ARs) and eight subtypes of P2Y receptors and to explore their potential for treating human disease conditions. (nih.gov)
  • I am a medicinal chemist with interests in the structure and pharmacology of receptors and in developing drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
  • Recent accomplishments include the design and synthesis of the highly potent and selective A3 adenosine receptor agonists and antagonists, using a combination of library screening and optimization of known adenosine receptor ligands. (nih.gov)
  • We have synthesized the first P2Y1 receptor-selective antagonists through functionalization of adenine nucleotides. (nih.gov)
  • The antagonists were optimized with the aid of receptor homology modeling. (nih.gov)
  • This study was undertaken in order to investigate the effect of chronic treatment with 5′-chloro-5′-deoxy-(±)-ENBA, a potent and highly selective agonist of human adenosine A 1 receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of the sciatic nerve. (mdpi.com)
  • Allosteric enhancer of A1 AR is found to be potent for the treatment of neuropathic pain, culminating the side effects related to off-target tissue activation of A1 AR. (eurekaselect.com)
  • The adenosine A 2B receptor (A 2B AR) has been identified as an important therapeutic target in cardiovascular disease, however in vitro and in vivo targeting has been limited by the paucity of pharmacological tools, particularly potent agonists. (monash.edu)
  • For A2A adenosine receptors CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadeno sine) and N-ethylcarboxamidoadenosine (NECA) were found to be the most potent agonists followed by R- and S-PIA with minor stereoselectivity. (biomedsearch.com)
  • NECA was the most potent agonist with an EC50-value of 2.3 microM whereas all other compounds tested were active at concentrations in the high micromolar range. (biomedsearch.com)
  • The N6-benzyl substituted derivatives of adenosine-5'-N-methyluronamide (MECA) turned out to be the most potent agonists. (biomedsearch.com)
  • Aki Y, Tomohiro A, Nishiyama A et al (1997) Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs. (springer.com)
  • Potent and highly selective agonist at A 1 adenosine receptors (K i values are 3.3, 9580, 37600 and 1150 nM for human recombinant A 1 , A 2A , A 2B and A 3 receptors respectively). (tocris.com)
  • Disclosed are (N)-methanocarba adenine nucleosides, e.g., of formula (I) as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. (nih.gov)
  • The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. (wikipathways.org)
  • Substances developed as potent and selective agents acting through adenosine and P2 receptors have proven useful as pharmacological probes and have potential for treating diseases of the central nervous system, immune system, and cardiovascular system. (nih.gov)
  • It is concluded that Thr277 contributes only to the binding of adenosine derivatives and that its role changes drastically with the receptor conformation and with the type of agonist (full or partial) interacting with the adenosine A1 receptors. (garvan.org.au)
  • There is provided exceptionally stable and useful pro-drugs that are esters of N6-oxa, thia, thioxa and azacycloalkyl substituted adenosine derivatives that are selective adenosine type 1 receptor agonists, and as such, are potentially useful agents for the treatment cardiovascular diseases and central nervous system disorders. (justia.com)
  • An object of this invention are novel pro-drugs of heterocyclic substituted adenosine derivatives. (justia.com)
  • Another object of this invention are pro-drugs of heterocyclic substituted adenosine derivatives that are converted in the mammalian body to become useful A1 receptor agonists. (justia.com)
  • Still another object of this invention are pro-drugs of heterocyclic substituted adenosine derivatives that are useful for treating supraventricular tachycardias, including atrial fibrillation, atrial flutter, and AV nodal re-entrant tachycardia in mammals and especially humans. (justia.com)
  • Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2. (nih.gov)
  • Adenosine is an organic compound that occurs widely in nature in the form of diverse derivatives. (wikipedia.org)
  • Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. (wikipedia.org)
  • CPA is widely used in scientific research into the adenosine receptors and has been used to derive a large family of derivatives. (wikipedia.org)
  • Both adenosine and xanthine derivatives bind competitively to A-1 and A-2 adenosine receptors. (patentgenius.com)
  • Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy In: ed Protein Reviews. (eurekaselect.com)
  • Adenosine was detected in the thalamic slices with an amperometric biosensor, and production by ectoATPases was confirmed by pharmacological inhibition. (sciencemag.org)
  • In this study all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). (biomedsearch.com)
  • The A1 subtype showed the typical pharmacological profile with 2-chloro-N6-cyclopentyladenosine (CCPA) as the agonist with the highest affinity and a marked stereoselectivity for the N6-phenylisopropyladenosine (PIA) diastereomers. (biomedsearch.com)
  • Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. (biomedsearch.com)
  • The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. (biomedsearch.com)
  • Relative importance of adenosine A1 and A3 receptors in mediating physiological or pharmacological protection from ischemic myocardial injury in the rabbit heart. (semanticscholar.org)
  • Boison D, Stewart K-A (2009) Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation. (springer.com)
  • This work provides a mechanism for the basis of acupuncture, as well as indicates that combining acupuncture with pharmacological inhibition of adenosine metabolism may expand the types of pain that acupuncture can alleviate. (sciencemag.org)
  • We are interested in correlating structure of receptors and small molecular drugs with pharmacological properties. (nih.gov)
  • The adenosine A 1 receptor (A 1 R) affinity and potency of these compounds was initially assessed using competitive binding assays and cyclic adenosine monophosphate (cAMP) accumulation assays in DDT 1 MF-2 cells. (wiley.com)
  • The thermodynamic parameters deltaGo (standard free energy), deltaHo (standard enthalpy) and deltaSo (standard entropy) of the binding equilibrium to rat brain receptors were determined by means of affinity measurements carried out at four different temperatures (0, 10, 20 and 25 degrees) and van't Hoff plots. (garvan.org.au)
  • Affinity constants were obtained from inhibition assays on membrane preparations of rat brain and CHO cells by use of the antagonist [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) as selective adenosine A1 receptor radioligand. (garvan.org.au)
  • As for human receptors, full agonist affinity was highly dependent on the presence of Thr277. (garvan.org.au)
  • Moreover, affinity to both wild-type and mutant receptors was enhanced by temperature increase, suggesting a totally entropy-driven binding. (garvan.org.au)
  • The bovine brain A1-adenosine receptor was purified 8000-fold by affinity chromatography on xanthine-amine-congener (XAC)-Sepharose. (biochemj.org)
  • In the presence of Go,i, about 20 and 40% of the receptors display guanine-nucleotide-sensitive high-affinity binding of the agonist radioligand (-)-N6-3-([125I]iodo-4-hydroxyphenylisopropyl)adenosine after reconstitution into lipid vesicles and in detergent solution, respectively. (biochemj.org)
  • Multivalent site-specific phage modification enhances the binding affinity of receptor ligands. (nih.gov)
  • The presence of allosteric modulators had diverse effects on the affinity of LUF5831, N6-cyclopentyladenosine (CPA), a full agonist, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an inverse agonist/antagonist, for the adenosine A1 receptor. (nih.gov)
  • In addition, LUF5831 was shown to have an affinity for the mutant (T277A) adenosine A1 receptor (Ki=122+/-22 nM), whereas CPA's affinity was negligible. (nih.gov)
  • The results of temperature-dependent binding assays showed that the binding of LUF5831 was entropy driven, in between the behaviour of CPA binding to the high- and low-affinity states of the receptor, respectively. (nih.gov)
  • In this study, by immunoprecipitation and affinity chromatography it is shown that adenosine deaminase and A1 adenosine receptors interact in pig brain cortical membranes. (nih.gov)
  • By means of this interaction adenosine deaminase leads to the appearance of the high-affinity site of the receptor, which corresponds to the receptor-G protein complex. (nih.gov)
  • In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. (biomedsearch.com)
  • The notion of xanthine-insensitivity of the A3 receptor should be dropped at least for the human receptor as xanthines with submicromolar affinity were found. (biomedsearch.com)
  • Regadenoson is an selective low-affinity (Ki= 1.3 µM) A2A receptor agonist that mimics the effects of adenosine in causing coronary vasodilatation and increasing myocardial blood flow. (drugbank.ca)
  • Furthermore, it has negligible affinity to A2B and A3 adenosine receptors. (drugbank.ca)
  • 2-Chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA)--a high affinity agonist radioligand for A1 adenosine receptors. (wikipathways.org)
  • In the rat, it has a 400- to 1800-fold greater affinity for A 1 than A 2α receptors ( 11 , 13 ). (asnjournals.org)
  • Stimulation of adenosine A1 receptors increases the affinity of dinucleotide receptors by five orders of magnitude, from 30 μM to 680 pM for control and in the presence of A1 agonist, respectively. (mendeley.com)
  • We validate that the interaction of VCP746 with the A 1 AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A 1 AR ligands. (pnas.org)
  • Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects. (pnas.org)
  • Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A 3 Receptor. (nih.gov)
  • Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
  • These cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands. (biomedsearch.com)
  • 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)
  • These can be quantified by determination of key parameters (left) and used to construct "Webs of Bias", an example of which is shown on the right for signalling of three different ligands at the adenosine A1 receptor. (monash.edu)
  • Novel ligands (small molecules) for these receptors are developed using classical synthetic approaches and also by semirational methods based on molecular modeling and template design. (nih.gov)
  • BACKGROUND: Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX) and PET. (rug.nl)
  • Addition of a 120-fold molar excess of a purified bovine brain G-protein preparation (Go,i a mixture of Go and Gi, containing predominantly Go) decreases the Bmax of the binding of the antagonist radioligand [3H]XAC to the receptor. (biochemj.org)
  • Radioligand binding experiments were performed in the absence and presence of diverse allosteric modulators on both wild-type (wt) and mutant (T277A) adenosine A1 receptors. (nih.gov)
  • In competition with antagonist radioligand biphasic curves were observed for agonists. (biomedsearch.com)
  • There are at least two subtypes of adenosine receptors in the heart: A1 and A2. (justia.com)
  • NECA was chosen for the study because caffeine is a nonselective adenosine receptor antagonist, and it is not known which of the four subtypes of adenosine receptors may be involved in an effect of caffeine on fatigue. (innovations-report.com)
  • Relative to the non-selective adenosine receptor agonist NECA, capadenoson was a biased A 2B AR agonist with a preference for cAMP signal transduction over other downstream mediators in cells with recombinant and endogenous A 2B AR expression. (monash.edu)
  • The A3 receptor was characterized utilizing the nonselective agonist [3H]NECA. (biomedsearch.com)
  • To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
  • Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (physiology.org)
  • Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (physiology.org)
  • The researchers' hypothesis is the foundation of a new study to determine the effects of intracerebroventricular injection of caffeine and the adenosine A1 and A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on treadmill run time to fatigue in rats. (innovations-report.com)
  • Abstract The purinergic receptor ligand, ATP, may participate in reflex induced vasoconstriction through sympathetic efferent and sensory afferent mechanisms. (medworm.com)
  • Adenosine is a purine nucleoside, responsible for the regulation of a wide range of physiological and pathophysiological conditions by binding with four G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B and A3 adenosine receptors (ARs). (eurekaselect.com)
  • The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). (pnas.org)
  • G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins and tractable drug targets ( 1 , 2 ). (pnas.org)
  • The adenosine receptors (or P1 receptors [1] ) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand . (wikipedia.org)
  • All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. (wikipedia.org)
  • Four adenosine receptor subtypes of the family of G protein-coupled receptors, designated A1, A2A, A2B and A3 are currently known. (biomedsearch.com)
  • Here, we overexpressed mouse DGK η in human embryonic kidney 293 cells to examine substrate specificity and signaling downstream of endogenous G protein-coupled receptors (GPCRs). (aspetjournals.org)
  • Dysregulation of G protein-coupled receptor (GPCR) activity is involved in the pathology of many psychiatric disorders, including BPD ( Catapano and Manji, 2007 ). (aspetjournals.org)
  • Human herpes virus KSHV encodes a constitutively active G‐protein‐coupled receptor linked to cell proliferation. (currentprotocols.com)
  • Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. (sciencemag.org)
  • G protein-coupled receptors (GPCRs) are a major target for hormones, neurotransmitters, and cytokines. (sciencemag.org)
  • G protein-coupled receptors (GPCRs) represent the largest family of receptor proteins encoded by the human genome and the biggest class of current drug targets. (monash.edu)
  • These findings have implications for understanding the role of adenosine and other extrahippocampal and intrahippocampal modulators in regulating SC synaptic function and the contributions of these modulators to the cognitive dysfunction associated with neuropsychiatric illnesses. (jneurosci.org)
  • The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. (deepdyve.com)
  • To address this, we utilize mutagenesis, biophysical techniques, x-ray crystallography and cutting edge computational modeling and docking methods to understand receptor dynamics and drug-receptor interactions, especially in the context of allosteric modulators and biased agonists. (monash.edu)
  • Our results demonstrated an involvement of adenosine A 1 receptor in the amplified nociceptive thresholds and in spinal glial and microglial changes occurred in neuropathic pain, without affecting motor coordination or blood pressure. (mdpi.com)
  • Our data suggest a possible use of adenosine A 1 receptor agonist in neuropathic pain symptoms. (mdpi.com)
  • Among several novel approaches that seem promising in relief of neuropathic pain, adenosine receptor agonists have attracted considerable attention. (asahq.org)
  • We recently published in collaboration with Daniela Salvemini of St. Louis University the protective effect of A3 agonists in animal models of neuropathic pain. (nih.gov)
  • We have discovered highly specific A3 agonists that reduce neuropathic pain in the mouse and rat and prevent its development. (nih.gov)
  • Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: the state of the art. (eurekaselect.com)
  • Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
  • In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. (biomedsearch.com)
  • ZM241385, DPCPX, MRS1706 are inverse agonists with different relative intrinsic efficacies on constitutively active mutants of the human adenosine A2B receptor. (wikipathways.org)
  • Valerian also contains isovaltrate, which has been shown to be an inverse agonist for adenosine A1 receptor sites. (visual-acuity.com)
  • In particular, A1 AR is ubiquitously present, mediating a variety of physiological processes throughout the body, thus represents a promising drug target for the management of various pathological conditions. (eurekaselect.com)
  • Adenosine-a physiological or pathophysiological agent? (eurekaselect.com)
  • Stimulation of the A1 adenosine receptor induces two distinct physiological responses. (justia.com)
  • Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. (semanticscholar.org)
  • As a breakdown product of ATP, adenosine is an endogenous purine nucleoside that modulates many physiological processes in all cells of the body. (physiology.org)
  • However, A2b and A3 receptors are relatively less active than A1 and A2a receptors under normal physiological conditions. (innovations-report.com)
  • Our research unexpectedly suggested that some of the physiological effects of AMP (and AMP analogs) might be due to direct activation of adenosine receptors and independent of ectonucleotidases. (painresearchforum.org)
  • Changes in tracer uptake after the administration of CPA resembled previously reported changes induced by treatment of rats with ethanol and an adenosine kinase inhibitor (ABT702). (rug.nl)
  • Insulin indirectly relieves GS inhibition ( 4 , 5 ) through a signaling cascade beginning with phosphorylation of substrates, including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor ( 6 , 7 ). (diabetesjournals.org)
  • Adenosine-mediated SC depotentiation does not involve activation of c-Jun N-terminal protein kinase, serine phosphatases, or nitric oxide synthase, unlike homosynaptic SC depotentiation. (jneurosci.org)
  • Since protein kinase C (PKC) can be activated by DAG and promotes receptor desensitization, we also examined functional interactions between PKC and DGK η . (aspetjournals.org)
  • To avoid these undesirable effects, indirect approaches, such as allosteric adenosine receptor modulation or inhibition of adenosine kinase 9,10 or adenosine deaminase, 11 have been examined and show antinociceptive effects in neuropathic rats. (asahq.org)
  • Boison D (2008) The adenosine kinase hypothesis of epileptogenesis. (springer.com)
  • Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gβγ complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. (sciencemag.org)
  • During simulated ischemia, cultured myocytes with enhanced expression of the human A3 receptor and showed significantly higher ATP content, fewer cells killed, and less creatine kinase released into the medium than either control or mock-transfected myocytes. (garvan.org.au)
  • Intracellular Receptor Modulation: Novel Approach to Target GPCRs. (nih.gov)
  • In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialog. (elsevier.es)
  • Among these indirect approaches, allosteric adenosine receptor modulation represents a novel drug development direction to potentiate A1 receptor function and agonist binding via a conformation change. (asahq.org)
  • Interaction of [3H]orphanin FQ and 125I‐tyr14‐orphanin FQ with the orphanin FQ receptor: Kinetics and modulation by cations and guanine nucleotides. (currentprotocols.com)
  • To assess the efficacy of the newly synthesized selective adenosine A 1 receptor agonist, BN-063 (1-cyclopropylisoguanosine), against myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. (elsevier.com)
  • Importantly, also in response to an adenosine A1 agonist, old rats had less sleep compared with young animals. (wiley.com)
  • These low molecular weight compounds activated glycogen synthase at ∼100 nmol/l in cultured CHO cells transfected with the insulin receptor and in primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. (diabetesjournals.org)
  • In the present studies, we examined mechanisms contributing to the effects of adenosine in hippocampal slices from male albino rats. (jneurosci.org)
  • ASP5854 ameliorated A(2A) agonist 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680)- and haloperidol-induced catalepsy in mice, with the minimum effective doses of 0.32 and 0.1 mg/kg, respectively, and it also improved haloperidol-induced catalepsy in rats at doses higher than 0.1 mg/kg. (curehunter.com)
  • 12,13 An adenosine receptor modulator, T62, belonging to a group of thiophene compounds first described a decade ago, 14 has been shown to reduce mechanical allodynia in spinal nerve-injured rats after oral, parenteral, or intrathecal application. (asahq.org)
  • Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. (wikipathways.org)
  • The natriuretic and diuretic action of a highly selective adenosine A 1 receptor (A 1 AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. (asnjournals.org)
  • Berman RF, Fredholm BB, Aden U, O'Connor WT (2000) Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats. (springer.com)
  • The main mechanism of action of caffeine in the brain seems to be a nonselective competitive blockade of adenosine receptors, in particular adenosine A1 receptors and A2A receptors ( Daly and Fredholm, 1998 ). (jneurosci.org)
  • Babich V, Vadnagara K, Di Sole F (2015) Dual effect of adenosine a1 receptor activation on renal O2 consumption. (springer.com)
  • Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A 1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. (elsevier.com)
  • Caffeine keeps you awake by blocking adenosine receptors. (wikipedia.org)
  • Methylxanthines (e.g. caffeine found in coffee, theophylline found in tea, or theobromine found in chocolate) have a purine structure and bind to some of the same receptors as adenosine. (wikipedia.org)
  • This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages. (jneurosci.org)
  • Caffeine, the adenosine A1 antagonist 8-cyclopentyltheophylline (CPT), and the adenosine A2A antagonist 5-amino-7-(2-phenylethyl)2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261) were administered intraperitoneally in all experiments. (jneurosci.org)
  • We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. (scielo.br)
  • Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O(2)C) were studied in awake mice lacking one or both of the adenosine A(1) or A(2A) receptors (A(1)R or A(2A)R, respectively) using telemetry and respirometry, before and after caffeine administration. (semanticscholar.org)
  • Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade. (semanticscholar.org)
  • Now, a team of researchers from the University of South Carolina has hypothesized that the blockade of adenosine receptors by caffeine may be the most likely mechanism of CNS stimulation and delayed fatigue. (innovations-report.com)
  • The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses. (sciencemag.org)
  • Ubiquitously expressed arrestin 2 and 3 (β arrestin 1 and 2) associate with agonist-evoked conformations of GPCRs that are phosphorylated by GRKs to mediate desensitization ( 3 , 4 ) and endocytosis via clathrin-coated pits ( 5 ). (sciencemag.org)
  • Spinophilin is a ubiquitously expressed protein containing an F-actin-binding domain, a phosphatase 1 (PP1) binding and regulatory domain, a protein-interaction PDZ domain, and C-terminal coiled-coil domains ( 9 , 10 ), and interacts with at least two subfamilies of GPCRs, the α 2 AR subtypes ( 11 ) and the D2 dopamine receptor ( 12 ). (sciencemag.org)
  • Receptors are computer-modeled by homology to GPCRs of known structure, and the models for ligand recognition are tested and refined using site-directed mutagenesis of the receptor proteins. (nih.gov)
  • Recently, the involvement of extracellular loops of GPCRs have been implicated in the receptor binding of small molecules. (nih.gov)
  • Rea MA , Pickard GE, (2000) 5-HT1B receptor agonist inhibits light-induced suppression of pineal melatonin production. (uh.edu)
  • Their theory is based on the fact that adenosine is produced within the body and inhibits neuronal excitability and synapse transmission. (innovations-report.com)
  • Adenosine also inhibits the release of most brain excitatory neurotransmitters, particularly dopamine (DA), and may reduce DA synthesis. (innovations-report.com)
  • Adenosine deaminase is an enzyme of purine metabolism that has largely been considered to be cytosolic. (nih.gov)
  • A few years ago, adenosine deaminase was reported to appear on the surface of cells. (nih.gov)
  • Recently, it has been demonstrated that adenosine deaminase interacts with a type II membrane protein known as either CD26 or dipeptidylpeptidase IV. (nih.gov)
  • Thus, it seems that adenosine deaminase is necessary for coupling A1 adenosine receptors to heterotrimeric G proteins. (nih.gov)
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (nih.gov)
  • Systemic inhibition of both AMP deaminase and adenosine deaminase, enzymes that metabolize these molecules, with deoxycoformycin (a clinically approved anticancer drug) prolonged the duration that local AMP and adenosine concentrations remained increased after acupuncture and enhanced the duration of the pain-relieving effects of acupuncture. (sciencemag.org)
  • The potency and receptor subtype selectivity of selected examples was further evaluated by measuring their effects on cAMP accumulation at all human adenosine receptor subtypes expressed in CHO cells. (wiley.com)
  • The cubanylmethyl derivative in particular proved to be highly receptor subtype selective. (wiley.com)
  • A1 subtype). (biomedsearch.com)
  • Another synthetic drug specific to the adenosine A2A receptor subtype is CGS-21680 that has been shown to cause apneas in 14- to 21-day-old rat pups in vivo. (wikipedia.org)
  • The A 1 adenosine receptor (A 1 AdoR) subtype is linked to inhibition of cAMP generation. (asnjournals.org)
  • Background Despite the clear cardioprotective effects of adenosine, when administered prior to ischemia, studies on cardioprotection by adenosine when administered at reperfusion have yielded contradictory results in both pre-clinical and clinical settings. (onlinejacc.org)
  • Thus, increasing the receptor level improves the myocyte sensitivity to the endogenous adenosine, which in turn causes all of the cardioprotective effects found for exogenously administered adenosine agonists. (garvan.org.au)
  • The authors concluded, "These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture. (thecamreport.com)
  • 1] "Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. (tcdb.org)
  • Adenosine is one of four nucleoside building blocks to DNA and RNA, which are essential for all life. (wikipedia.org)
  • In this regard, the level of nucleoside adenosine is increased in individuals with obesity. (elsevier.es)
  • Effects of adenosine on tubular transport are most pronounced in the proximal tubule where the nucleoside stimulates NaCl reabsorption in the subnormal concentration range while inhibiting transport at elevated levels. (springer.com)
  • Because adenosine production increases in hypoxia, the issue of a role of the nucleoside in the renal injury following ischemia reperfusion has been studied extensively. (springer.com)
  • The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. (springer.com)
  • Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5′-nucleotidase. (springer.com)
  • Interactions of purified bovine brain A1-adenosine receptors with G-proteins. (biochemj.org)
  • The ability of Go,i to enhance agonist binding and decrease antagonist binding is concentration-dependent, with a half-maximal effect occurring at approximately 10-fold molar excess of G-proteins over A1-adenosine receptors. (biochemj.org)
  • These results show (1) that detergent removal is not a prerequisite for the observation of coupling between the A1-adenosine receptor and Go,i, and (2) that the regulatory effect of G-proteins on antagonist binding to the A1-adenosine receptor can be reconstituted by using purified components. (biochemj.org)
  • Antagonist exposure (1) increased the density of A 1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. (elsevier.com)
  • Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
  • The concepts of the receptor and receptor theory, based on the Law of Mass Action, have undergone continuous refinement as they have been characterized in terms of their molecular structure, association with ancillary proteins (e.g. (currentprotocols.com)
  • Expanding horizons for receptors coupled to G proteins: Diversity and disease. (currentprotocols.com)
  • In this regard, partial agonists of A1 AR have been found to be beneficial in enhancing insulin sensitivity and subsequently reducing blood glucose level, while avoiding severe CVS side effects and tachyphylaxis. (eurekaselect.com)
  • Stimulation of the adenosine A1 receptor accordingly shortens the duration and decreases the amplitude of the action potential of AV nodal cells and subsequently prolongs the refractory period of the cells. (justia.com)
  • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. (nih.gov)
  • We previously found that low-frequency stimulation of direct temperoammonic (TA) inputs to hippocampal area CA1 depotentiates previously established long-term potentiation in the Schaffer collateral (SC) pathway through complex signaling involving dopamine, endocannabinoids, neuregulin-1, GABA, and adenosine, with adenosine being the most distal modulator identified to date. (jneurosci.org)
  • provide evidence that one mechanism by which DBS reduces tremor is through stimulation of nonsynaptic release of adenosine triphosphate (ATP). (sciencemag.org)
  • The release of ATP was deemed to be nonsynaptic, because it did not require calcium and removal of extracellular calcium increased the accumulation of adenosine in response to high-frequency stimulation. (sciencemag.org)
  • The role of the A1 receptor and adenosine was also confirmed by showing that high-frequency stimulation failed to reduce evoked excitatory postsynaptic potentials (eEPSPs) in the presence of an A1 receptor antagonist or an inhibitor of ectoATPase activity. (sciencemag.org)
  • Application of adenosine or an A1 receptor agonist reduced eEPSP amplitude in the absence of high-frequency stimulation. (sciencemag.org)
  • In slices from mice deficient for A1 receptors, high-frequency stimulation failed to reduce eEPSP amplitude. (sciencemag.org)
  • Deep brain stimulation appears to trigger nonsynaptic release of ATP, which when converted to adenosine contributes to the tremor-reducing effects of this treatment. (sciencemag.org)
  • Thus, any blockade of A 2 Ado receptors could reduce the GFR and sodium excretion (U Na V) and also may cause unwanted cardiac stimulation and increases in BP ( 14 ). (asnjournals.org)
  • Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of α 2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. (sciencemag.org)
  • A thermodynamic analysis of the binding of a full agonist (N6-cyclopentyladenosine), a partial agonist (8-butylamino-N6-cyclopentyladenosine) and an antagonist (8-cyclopentyltheophylline) to human wild-type and mutant (mutation of a threonine (Thr) to an alanine (Ala) residue at position 277) adenosine A1 receptors expressed on Chinese hamster ovary (CHO) cells, and to rat brain adenosine A1 receptors was undertaken. (garvan.org.au)
  • As for rat brain receptors, full agonist binding was totally entropy driven, whereas antagonist binding was essentially enthalpy driven. (garvan.org.au)
  • One of these AMP analogs was orally active and had A1-dependent antinociceptive effects in mice with minimal to no cardiovascular side effects. (painresearchforum.org)
  • Given our finding that AMP and AMP analogs can signal directly through adenosine A1 receptors, this raises the question of whether chet-AMP is also an A1 agonist. (painresearchforum.org)
  • An adenosine A1 receptor agonist has been shown to depress preBötC rhythmogenesis independent of the neurotransmitters GABA and glycine in in vitro preparations from 0-7 day old mice. (wikipedia.org)
  • Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupuncture. (ogka.at)
  • All of these effects are obliterated in knockout genetic strains of mice which lack the adenosine A1 receptor. (chiroaccess.com)
  • Adenosine, a neuromodulator with anti-pain properties, was released during acupuncture in mice. (thecamreport.com)
  • 2002). 5-HT1B receptor knockout mice exhibit an enhanced response to constant light. (uh.edu)
  • Borowicz KK, Luszczki J, Czuczwar SJ (2002) 2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice. (springer.com)
  • found that acupuncture at the "Zusanli" point (near the knee) in mice produced nociception and increased the local concentrations of adenine nucleotides (ATP, ADP, and AMP) and adenosine. (sciencemag.org)
  • We recently found an A1 adenosine receptor agonist that has antiseizure effects in mice without some of the side effects associated with such agonists in the past. (nih.gov)
  • This is a direct effect on pacemaker cells and is mediated by extracellular adenosine receptors (i.e. (biomedsearch.com)
  • We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. (physiology.org)
  • During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. (springer.com)
  • In addition, overexpression of DGK η enhanced calcium mobilization after stimulating muscarinic receptors with carbachol and after stimulating purinergic receptors with ATP. (aspetjournals.org)
  • Adenosine-dependent regulation of renal function in healthy and diseased kidney is mediated by activation of the four types of P1 purinergic adenosine receptors (A 1 AR, A 2A AR, A 2B AR, A 3 AR). (springer.com)
  • Purinergic receptor antagonism: A viable strategy for the management of autonomic dysreflexia? (medworm.com)
  • However, treatment with full A1 AR agonists has been associated with numerous challenges like cardiovascular side effects, off-target activation as well as desensitization of A1 AR leading to tachyphylaxis. (eurekaselect.com)
  • The mechanisms of otoprotection by Adenosine amine congener include inhibition of glutamate release via presynaptic A1 receptors and inhibition of voltage-gated Ca 2+ channels, which can prevent activation of apoptotic and necrotic cell death pathways [1] . (medchemexpress.com)
  • The results of this study demonstrate that BN-063, through activation of adenosine A 1 receptors, exerts antiarrhythmic and anti-infarct effects during myocardial ischemia-reperfusion. (elsevier.com)
  • Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory. (wikipedia.org)
  • Adenosine and acetylcholine have similar effects, being additive up to a maximal response, and may be the result of activation of the same K+ channels via different receptors. (biomedsearch.com)
  • The present results indicate that TA-induced depotentiation requires intact inputs from entorhinal cortex and that adenosine ultimately drives depotentiation via activation of p38 MAPK. (jneurosci.org)
  • This form of heterosynaptic resetting engages complex signals that include activation of dopamine (DA) D4 receptors (D4Rs), endocannabinoid CB1 receptors (CB1Rs), ErbB4 receptors, GABA A receptors (GABA A Rs), and adenosine A1 receptors (A1Rs), likely in that order ( Izumi and Zorumski, 2008 , 2016 , 2017 ). (jneurosci.org)
  • Conversion of ATP to adenosine by ectoATPases then stimulates the activation of A1 receptors. (sciencemag.org)
  • We found that activation of adenosine receptors affected the proliferation of NPCs. (deepdyve.com)
  • The A2a-adenosine system decreases activation and cytokine release in immune cells. (deepdyve.com)
  • however, activation of the A2a receptor downregulated cell proliferation and cytokine release. (deepdyve.com)
  • Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATP channel activation. (semanticscholar.org)
  • Moreover, adenosine protects against renal ischemic reperfusion injury by the anti-inflammatory effect of enhancing the activity of regulatory T cell and by attenuating the inflammatory injury produced by neutrophils via A 2 AR activation. (springer.com)
  • Al-Mashhadi RH, Skott O, Vanhoutte PM et al (2009) Activation of A(2) adenosine receptors dilates cortical efferent arterioles in mouse. (springer.com)
  • Awad AS, Huang L, Ye H et al (2006) Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy. (springer.com)
  • Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
  • Adenosine modulates the preBötC output via activation of the A1 and A2A receptor subtypes. (wikipedia.org)
  • We have used convergent modeling, mutagenesis and structure activity approaches to gather information about the three-dimensional structure of the receptors and its relationship to binding and activation functions. (nih.gov)
  • Selective Activation of Adenosine A2A Receptors on Immune Cells by a CD73-Dependent Prodrug Suppresses Joint Inflammation in Experimental Rheumatoid Arthritis. (painresearchforum.org)
  • Activation did not require hydrolysis of AMP to adenosine by ectonucleotidases. (painresearchforum.org)
  • Flögel and colleagues reported that the anti-inflammatory effects of chet-AMP were due to hydrolysis to chet-adenosine by ecto-5'-nucleotidase (NT5E, also known as CD73) followed by activation of the adenosine A2A receptor. (painresearchforum.org)
  • [3] For instance, both A 1 receptors and A 2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A 2A receptor also has broader anti-inflammatory effects throughout the body. (wikipedia.org)
  • Enzymatic production of adenosine can be anti-inflammatory or immunosuppressive. (wikipedia.org)
  • Although, adenosine activating its receptors (A 1 , A 2A , A 2B and A 3 ) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. (elsevier.es)
  • The A2AR is expressed in lung tissues, where it is activated by endogenous/exogenous adenosine or A2AR agonists and where it exerts anti-inflammatory effects ( 24 , 39 , 45 ). (physiology.org)
  • And related, are the anti-inflammatory effects seen in vivo A1 and/or A2A mediated? (painresearchforum.org)
  • Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia, ischemia, and seizure activity. (wikipedia.org)
  • This study investigated whether aldose reductase (AR) inhibition with zopolrestat, either alone or in combination with an adenosine A(3)-receptor agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion. (semanticscholar.org)
  • Experimental evidence supports the notion that adenosine protects against ischemia-induced acute kidney injury by directly acting on renal endothelial and tubular A 1 AR. (springer.com)
  • It has been shown that an A2AR agonist protects against ischemia-reperfusion injury in porcine allogeneic lung transplantation ( 23 ). (physiology.org)
  • These nucleosides exhibit similar selectivities as agonists of the A3 versus the A1 receptor for both human and mouse adenosine receptors, and are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. (nih.gov)
  • Adenosine is an important mediator of the endogenous defense against ischemia-induced injury in the heart. (garvan.org.au)
  • Adenosine can achieve cardioprotection by mediating the effect of ischemic preconditioning and by protecting against myocyte injury when it is present during the infarct-producing ischemia. (garvan.org.au)
  • The objective of the present study was to investigate whether genetic manipulation of the cardiac myocyte, achieved by gene transfer and overexpression of the human A3 receptor cDNA, renders the myocytes resistant to the deleterious effect of ischemia. (garvan.org.au)
  • Prolonged hypoxia with glucose deprivation, causing myocyte injury and adenosine release, was used to simulate ischemia in cultured chick embryo ventricular myocytes. (garvan.org.au)
  • Also, increased expression of the A3 receptor caused an enhanced cardioprotective effect by the preconditioning ischemia. (garvan.org.au)
  • Overexpressing the adenosine A1 receptor also led to increased protection against ischemia-induced myocyte injury as well as an enhanced preconditioning effect. (garvan.org.au)
  • Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3). (wikipedia.org)
  • Thus, the administration of an exogenous agonist or increasing the level of an endogenous agonist have similar effects. (rug.nl)
  • Borea PA, Gessi S, Merighi S, Varani K. Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? (eurekaselect.com)
  • Adenosine amine congener also has neuroprotective effects. (medchemexpress.com)
  • A1 agonists, through their ability to inhibit the catecholamine induced increase in cAMP, should have beneficial effects in the failing heart where increased sympathetic tone causing enhanced cAMP has been associated with increased likelihood of ventricular arrhythmias and sudden death. (justia.com)
  • the hypothesis is that this bitopic mode would result in unique receptor conformations that will signal to desirable pathways while sparing those pathways mediating undesirable effects. (pnas.org)
  • Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. (wikipedia.org)
  • The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. (wikipedia.org)
  • These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. (jneurosci.org)
  • Agmon Y, Dinour D, Brezis M (1993) Disparate effects of adenosine A1- and A2-receptor agonists on intrarenal blood flow. (springer.com)
  • Beach RE, Good DW (1992) Effects of adenosine on ion transport in rat medullary thick ascending limb. (springer.com)
  • Beach RE, Watts BA 3rd, Good DW et al (1991) Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions. (springer.com)
  • Several studies have also suggested that the beneficial effects of adenosine occur through the effects of the A2AR and A2BR ( 7 , 22 , 27 , 43 ). (physiology.org)
  • Objectives In the absence of effective clinical pharmacotherapy for prevention of reperfusion-mediated injury, this study re-evaluated the effects of intracoronary adenosine on infarct size and no-reflow in a porcine model of acute myocardial infarction using clinical bolus and experimental high-dose infusion regimens. (onlinejacc.org)
  • These multiple physiologic functions controlled by adenosine receptors result in some undesirable side effects from direct adenosine receptor agonists, including headache, nausea, 5 motor weakness, 6,7 chest pain, and atrioventricular block, 8 which limit their clinical application. (asahq.org)
  • However, it exerts selective, and often antagonistic, effects on cell function mediated through a family of adenosine receptors. (asnjournals.org)
  • All of these findings clearly demonstrate that (1) adenosine mediates the effects of acupuncture, and (2) interfering with adenosine breakdown may prolong the clinical effects of acupuncture. (chiroaccess.com)
  • What this elegant series of experiments has shown us is that, at least for one type of acupuncture executed in an animal model, the analgesic effects most commonly attributed to acupuncture have been packaged into a functional receptor for a neurotransmitter. (chiroaccess.com)
  • Receptors, located on both the cell surface and within the cell, are the molecular targets through which drugs produce their beneficial effects in various disease states. (currentprotocols.com)
  • Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A 1 adenosine receptor expression. (elsevier.com)
  • In addition, cyclic adenosine monophosphate (cAMP) assays were performed. (nih.gov)
  • Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. (wikipedia.org)
  • In the current study, we have rationally designed a novel A 1 AR ligand (VCP746)-a hybrid molecule comprising adenosine linked to a positive allosteric modulator-specifically to engender biased signaling at the A 1 AR. (pnas.org)
  • The interaction of a new nonribose ligand (LUF5831) with the human adenosine A1 receptor was investigated in the present study. (nih.gov)
  • This study indicates that the nonribose ligand, LUF5831, is a partial agonist for the adenosine A1 receptor. (nih.gov)
  • This is the first report in brain demonstrating an interaction between a degradative ectoenzyme and the receptor whose ligand is the enzyme substrate. (nih.gov)
  • Chimaeric nicotinic: Serotonergic receptor combines distinct ligand binding and channel specificities. (currentprotocols.com)
  • NICE 2011) Drugs used to treat hypertension include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium-channel blockers, diuretics and beta-blockers. (acupuncture.org.uk)
  • Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes. (semanticscholar.org)
  • We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. (deepdyve.com)
  • Chronic systemic administration of 5′-chloro-5′-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A 1 adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. (mdpi.com)
  • The in vivo EC 50,u values for the reduction in HR (366 nM, 210 nM, 170 nM and 175 nM for 8MCPA, 8ECPA, 8PCPA and 8BCPA, respectively) were in the same order of magnitude as the affinities in receptor binding studies. (aspetjournals.org)
  • In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. (wikipathways.org)
  • Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. (wikipathways.org)
  • To ascertain receptor mechanism, Flögel and colleagues used only one A2A antagonist (KW-6002) at a single concentration in vivo (delivered continuously for 1-2 weeks using an osmotic minipump). (painresearchforum.org)
  • high resolution crystal structure of the M2 muscarinic acetylcholine receptor bound to an activating nanobody (Nb9-8, green), orthosteric agonist (iperoxo, yellow) and positive allosteric modulator (LY2119620, purple). (monash.edu)
  • movie showing molecular dynamics simulation of a negative allosteric modulator drug binding to the M2 muscarinic acetylcholine receptor. (monash.edu)
  • Subsequent triggering of chemokine receptors through chemokines then activates leukocyte integrins and allows firm adhesion of the cell. (ahajournals.org)
  • Target selectivity is defined as a difference in target binding to different receptors, and tissue selectivity is defined as a difference in target binding to the same target in different tissues. (springer.com)
  • CONCLUSION: Small-animal PET with (11)C-MPDX can be used to assess antagonist but not agonist binding at A1Rs. (rug.nl)
  • Barrett RJ, Droppleman DA (1993) Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. (springer.com)
  • In the striatum, adenosine plays an important role as a modulator of both dopamine and glutamate neurotransmission. (jneurosci.org)
  • The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. (wikipedia.org)
  • 2001) Adenosine1 receptor agonists inhibit photic phase shifts of the circadian activity rhythm in hamsters. (uh.edu)
  • 1996) 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene, c-fos, in the suprachiasmatic nucleus. (uh.edu)