Adenosine: 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.Receptor, Adenosine A2A: 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.Receptor, Adenosine A1: 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.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Receptor, Adenosine A3: 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.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Receptor, Adenosine A2B: 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.Receptors, Purinergic P1: 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).Receptors, Adenosine A2: 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.Adenosine Kinase: 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.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Serotonin Receptor Agonists: 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.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Serotonin 5-HT1 Receptor Agonists: 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.Xanthines: Purine bases found in body tissues and fluids and in some plants.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Serotonin 5-HT2 Receptor Agonists: 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.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).GABA-A Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.Receptors, Purinergic: 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.Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.Serotonin 5-HT4 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.Rats, Sprague-Dawley: 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.Cyclic AMP: 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.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.Theophylline: 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.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.2-Chloroadenosine: 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.Receptors, Opioid, kappa: 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.Histamine Agonists: 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.Muscarinic Agonists: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Receptors, Opioid, mu: 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.Receptors, Dopamine D2: 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.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine: A selective D1 dopamine receptor agonist used primarily as a research tool.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Baclofen: 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.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Quinpirole: A dopamine D2/D3 receptor agonist.5'-Nucleotidase: 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.Nicotinic Agonists: 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.Receptors, Opioid, delta: 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.Receptors, Dopamine D1: 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.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Cells, Cultured: 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.Inosine: 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)Piperidines: A family of hexahydropyridines.Guinea Pigs: 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.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Benzazepines: Compounds with BENZENE fused to AZEPINES.Calcium: 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.8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.Enkephalin, Ala(2)-MePhe(4)-Gly(5)-: An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Cannabinoids: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Tubercidin: 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.Receptors, Opioid: 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.Theobromine: 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)Muscimol: 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.Serotonin: 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.Receptors, Serotonin: 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.PyrrolidinesAdenosine Triphosphatases: 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.Naphthalenes: 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.Adenine NucleotidesReceptors, Purinergic P2: 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.Triazines: 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.Signal Transduction: 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.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.Purinergic P2Y Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.Kinetics: The rate dynamics in chemical or physical systems.Dopamine Antagonists: 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.Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.Isoproterenol: 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.Receptors, Glucagon: 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.Benzoxazines: OXAZINES with a fused BENZENE ring.Purinergic P2X Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.Receptor, Cannabinoid, CB2: A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Neurons: 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.Venoms: 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.Serotonin 5-HT3 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT3 RECEPTORS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ligands: 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)Behavior, Animal: The observable response an animal makes to any situation.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Purinergic Agonists: Compounds that bind to and activate PURINERGIC RECEPTORS.PiperazinesColforsin: 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.Mice, Inbred C57BLPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Apomorphine: 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.Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.Purines: 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.Indoles: 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.Binding, Competitive: 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.Receptors, Dopamine D3: A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.Ergolines: A series of structurally-related alkaloids that contain the ergoline backbone structure.Enkephalins: 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.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Methylhistamines: Histamine substituted in any position with one or more methyl groups. Many of these are agonists for the H1, H2, or both histamine receptors.Dopamine: 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.Dipyridamole: 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)Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Receptor, Serotonin, 5-HT1B: 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.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptors, Serotonin, 5-HT4: 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.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.MorpholinesBenzeneacetamides: Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.Receptors, sigma: 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.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Receptors, Prostaglandin E: 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.CHO Cells: 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.TriazolesReceptor, Serotonin, 5-HT1A: 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.Synaptic Transmission: 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.Receptors, Metabotropic Glutamate: 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.Coformycin: A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.Receptors, Histamine: 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.Bicyclo CompoundsReceptor, Serotonin, 5-HT2A: 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.Receptors, Dopamine: Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Receptors, Histamine H3: 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)Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Receptors, Drug: 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.Norepinephrine: 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.Muscle, Smooth: 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)Histamine: 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.Bicyclo Compounds, Heterocyclic: 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)Disease Models, Animal: 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.Impromidine: A highly potent and specific histamine H2 receptor agonist. It has been used diagnostically as a gastric secretion indicator.Receptor, Serotonin, 5-HT2C: 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.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.Patch-Clamp Techniques: 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.Rabbits: 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'-O-(3-Thiotriphosphate): 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.Receptors, Histamine H2: 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)Mice, Knockout: 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.Fenoldopam: A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.RNA, Messenger: 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.Membrane Potentials: 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).Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Amphetamines: 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.Naltrexone: 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.GTP-Binding Proteins: 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.-.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Pentostatin: 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.Receptors, Adrenergic, beta: 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.Dogs: 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)Imidazoles: 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).Cyclic AMP-Dependent Protein Kinases: 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.Hydrocarbons, FluorinatedAdenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Receptors, Muscarinic: 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.Corpus Striatum: 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.Thioinosine: 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)Adenosine Phosphosulfate: 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.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Structure-Activity Relationship: 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.Microdialysis: 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.QuinoxalinesPertussis Toxin: 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.Receptors, Adrenergic, alpha-2: 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.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Substance P: 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.Hippocampus: 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.Rats, Inbred Strains: 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.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Dronabinol: 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.Receptors, GABA-A: 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.Cyclohexanols: 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.Electrophysiology: 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.Receptors, Serotonin, 5-HT1: A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.

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)

*Adenosine receptor

Tecadenoson is an effective A1 adenosine agonist, as is selodenoson. The A1, together with A2A receptors of endogenous ... The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as endogenous ... The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. This receptor has an inhibitory function ... Adenosine receptors play a key role in the homeostasis of bone. The A1 receptor has been shown to stimulate osteoclast ...

*Adenosine A2A receptor

"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 ...

*Adenosine A3 receptor

... 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 ...

*N6-Cyclopentyladenosine

... 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 ...

*Dipropylcyclopentylxanthine

"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 ...

*CCPA (biochemistry)

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. ...

*Valerian (herb)

Valerian also contains isovaltrate, which has been shown to be an inverse agonist for adenosine A1 receptor sites. This action ... 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. ...

*Adenosine A1 receptor

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 ...

*Pre-Bötzinger complex

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 ...

*CPA

... an adenosine A1 receptor agonist Cyclophosphamide Cyclopropane fatty acid, a component of some rare fats Cation:Proton ...

*Adenosine

"Anti-Inflammatory Preconditioning by Agonists of Adenosine A1 Receptor". PLoS ONE. 3 (5): e2107. Bibcode:2008PLoSO...3.2107N. ... 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 ...

*Caffeine-induced anxiety disorder

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 ...

*PSB-10

... 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 ...

*5-HT2A receptor

... 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 ... The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G ... 5-HT2C receptor distribution TCB-2 Mexamine is a full agonist to several serotonin receptors. O-4310, 5-HT2A selective, claimed ...

*Pharmacodynamics

... 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 ... receptor reserve is an integrative measure of the response-inducing capacity of an agonist (in some receptor models it is ... Hormone receptors Neuromodulator receptors Neurotransmitter receptors General anesthetics were once thought to work by ...

*Adenosine A2B receptor

"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 ...

*5-HT1D receptor

"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. ...

*Dopamine receptor

... adenosine A1 D1-D2 dopamine receptor heteromer D1-D3 dopamine receptor heteromer D2-D4 dopamine receptor heteromer D2-adenosine ... unless blocked by a receptor antagonist or a synthetic partial agonist. D3 is encoded by the Dopamine receptor D3 gene (DRD3). ... The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are ... Additionally, many antipsychotic drugs target dopamine receptors, especially D2 receptors. Dopamine receptor mutations can ...

*Gliotransmitter

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- ...

*Caffeine

... 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 ...

*Purinergic signalling

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 ...

*Basal ganglia

... muscarinic acetylcholine receptor M4, and adenosine receptor A1. The direct pathway has been proposed to facilitate motor ... This model of direct D1, and indirect D2 pathways explain why selective agonists of each receptor are not rewarding, as ... This pathway consists of MSNs that express dopamine receptor D2, muscarinic acetylcholine receptor M1, and adenosine receptor ... "Adenosine-cannabinoid receptor interactions. Implications for striatal function". British Journal of Pharmacology. 160 (3): 443 ...

*Theophylline

... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...

*Heteroreceptor

"Control of Cannabinoid CB1 Receptor Function on Glutamate Axon Terminals by Endogenous Adenosine Acting at A1 Receptors". ... Ma, D.; Rajakumaraswamy, N.; Maze, M. (2004). "2-Adrenoceptor agonists: Shedding light on neuroprotection?". British Medical ... "Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: ... A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own ligand. ...

*Nucleus accumbens

... they also express adenosine A1 receptors), while dynorphinergic MSNs connect the striatum with the substantia nigra (pars ... GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABAA receptors in the NAc shell have ... and express the peptides dynorphin and substance P and dopamine D1 and adenosine A1 but not A2A receptors ... These two ... It has been demonstrated that D1 receptors form the hetero-oligomer with D2 receptors, and that the D1-D2 receptor hetero- ...

*G protein-coupled receptor

"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). More recently, an alternative ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors ( ... G protein-coupled receptors database List of MeSH codes (D12.776) Metabotropic receptor Orphan receptor Pepducins, a class of ...
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.
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
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
The National Training Authority (NTA) was formed because The Gambia like other developing nations understood the need to support its national development process through the creation of a Skills Development Strategy. This page includes its contact address, telephone number, fax and main office location.
A series of 5-carbamoyl and 5-thionocarbamoyl derivatives of 2-C-methyl analogues of the A(1) adenosine receptor (A(1)AR) full agonists N(6)-cyclopentyladenosine (CPA), 2-chloro-N(6)-cyclopentyladenosine (CCPA), N(6)-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N(6)-cyclopentylamino series, the 5-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N(6)-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine A(1)AR. The 5-methylthionocarbamoyl derivative of 2-Me-CCPA showed the best affinity at porcine A(1)AR with a K(i) value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at A(1)AR and very ...
The IUPHAR/BPS Guide to Pharmacology. cyclopentyladenosine ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
36396-99-3 - SZBULDQSDUXAPJ-WXURJZIFSA-N - N(6)-Cyclohexyladenosine - Similar structures search, synonyms, formulas, resource links, and other chemical information.
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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 ...
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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methyl 2-cyclopentyl-2-(methoxycarbonylamino)acetate - chemical structural formula, chemical names, chemical properties, synthesis references
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Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
BioAssay record AID 33566 submitted by ChEMBL: Inhibition of [3H]5-(N-ethylcarbamoyl)-adenosine binding to adenosine A2 receptor in rat striatal membranes with 50 nM cyclopentyladenosine.
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 ...

MilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA 25mg:LifeMilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA 25mg:Life

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 ...
more infohttps://www.fishersci.com/shop/products/calbiochem-adenosine-a1-receptor-agonist-i-cpa/11913525MG

Synthesis and Biological Evaluation of Adenosines with Heterobicyclic and Polycyclic N6-Substituents as Adenosine A1 Receptor...Synthesis and Biological Evaluation of Adenosines with Heterobicyclic and Polycyclic N6-Substituents as Adenosine A1 Receptor...

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 ...
more infohttp://onlinelibrary.wiley.com/doi/10.1002/cmdc.201200208/full

Molecules | Free Full-Text | 5-Chloro-5-deoxy-(±)-ENBA, a Potent and Selective Adenosine A1 Receptor Agonist, Alleviates...Molecules | Free Full-Text | 5'-Chloro-5'-deoxy-(±)-ENBA, a Potent and Selective Adenosine A1 Receptor Agonist, Alleviates...

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 ...
more infohttp://mdpi.com/1420-3049/17/12/13712/xml

Optimization of thermolytic response to A1 adenosine receptor agonists in rats | Journal of Pharmacology and Experimental...Optimization of thermolytic response to A1 adenosine receptor agonists in rats | Journal of Pharmacology and Experimental...

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 ...
more infohttp://jpet.aspetjournals.org/content/early/2017/06/26/jpet.117.241315/tab-article-info

Thermodynamics of full agonist, partial agonist, and antagonist binding to wild-type and mutant adenosine A1 receptors | Garvan...Thermodynamics of full agonist, partial agonist, and antagonist binding to wild-type and mutant adenosine A1 receptors | Garvan...

... 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 ...
more infohttps://www.garvan.org.au/research/publications/1161

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...

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 ...
more infohttp://www.biochemj.org/content/275/3/651?ijkey=2315fd1b806ff30b6970ab77aeda8bbc35ec77ac&keytype2=tf_ipsecsha

A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes | Journal of...A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes | Journal of...

A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes ... A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes. Marjan Fatholahi, ... A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes. Marjan Fatholahi, ... A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes. Marjan Fatholahi, ...
more infohttp://jpet.aspetjournals.org/content/317/2/676

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...

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 ...
more infohttps://repository.up.ac.za/handle/2263/29077

COMPOSITIONS AND METHODS FOR MODULATING AUTOPHAGY - SAN DIEGO STATE UNIVERSITY (SDSU) FOUNDATIONCOMPOSITIONS AND METHODS FOR MODULATING AUTOPHAGY - SAN DIEGO STATE UNIVERSITY (SDSU) FOUNDATION

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, ...
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adenosine 5-monophosphate (CHEBI:16027)adenosine 5'-monophosphate (CHEBI:16027)

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- ...
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adenosine 5-monophosphate (CHEBI:16027)adenosine 5'-monophosphate (CHEBI:16027)

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- ...
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Full text] Current treatments for acute heart failure: focus on serelaxin | RRCCFull text] Current treatments for acute heart failure: focus on serelaxin | RRCC

Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal. 2012;8(Suppl 1):91-99. ... Among the adenosine A1 receptor blockers developed, rolofylline has the lowest specificity for the A1 receptor, with 32-fold ... known as the A1, A2a, A2b, and A3 receptors.43,44 In the kidney, adenosine activates the A1 receptor to cause vasoconstriction ... Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010;363(15):1419-1428. ...
more infohttps://www.dovepress.com/current-treatments-for-acute-heart-failure-focus-on-serelaxin-peer-reviewed-fulltext-article-RRCC

A<sub>1</sub> Adenosine Receptor Activation Inhibits Inflammation, Necrosis, and Apoptosis after Renal Ischemia-Reperfusion...A<sub>1</sub> Adenosine Receptor Activation Inhibits Inflammation, Necrosis, and Apoptosis after Renal Ischemia-Reperfusion...

C57BL/6 mice that had been pretreated with the A1 AR agonist demonstrated significantly improved renal function and reduced ... T1 - A1 Adenosine Receptor Activation Inhibits Inflammation, Necrosis, and Apoptosis after Renal Ischemia-Reperfusion Injury in ... title = "A1 Adenosine Receptor Activation Inhibits Inflammation, Necrosis, and Apoptosis after Renal Ischemia-Reperfusion ... N2 - It was previously demonstrated that preischemic A1 adenosine receptor (AR) activation protects renal function after ...
more infohttps://mayoclinic.pure.elsevier.com/en/publications/asub1sub-adenosine-receptor-activation-inhibits-inflammation-necr

Featured Articles : Cardiology in ReviewFeatured Articles : Cardiology in Review

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 ...
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JCI -
Volume 115, Issue 3JCI - Volume 115, Issue 3

... the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABAA receptor modulators diazepam, ... In this study we observed that administration of Toll-like receptor 9 (TLR9) agonists suppressed the severity of experimental ... Here, we have identified PGE2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory ... In this issue of the JCI, the gene coding for the γ-aminobutyric acidA (GABAA) receptor α1 subunit is suggested as a potential ...
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Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation, Brain Research | 10.1016/j.brainres...Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation, Brain Research | 10.1016/j.brainres...

"Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation, Brain Research" on DeepDyve, the ... We found that activation of adenosine receptors affected the proliferation of NPCs.•The A1 and A2a adenosine receptor agonists ... We found that activation of adenosine receptors affected the proliferation of NPCs.•The A1 and A2a adenosine receptor agonists ... Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation. Activation of A1 and A2a adenosine ...
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US Patent # 9,833,448. Piperidinone carboxamide azaindane CGRP receptor antagonists - Patents.comUS Patent # 9,833,448. Piperidinone carboxamide azaindane CGRP receptor antagonists - Patents.com

The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and ... an adenosine A1 receptor agonist; a sodium channel blocker, for example lamotrigine; an opiate agonist such as levomethadyl ... an alpha receptor agonist; a vanilloid receptor antagonist; a renin inhibitor; a granzyme B inhibitor; a substance P antagonist ... sup.125I-CGRP to receptors and functional antagonism of CGRP receptors were determined as follows: Native Receptor Binding ...
more infohttp://patents.com/us-9833448.html

HypertensionHypertension

Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes ... Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 2010; May 30. ... and that its anti-nociceptive actions required adenosine A1 receptor expression. ... A study showing that the neuromodulator adenosine, which has anti-nociceptive properties, was released during acupuncture in ...
more infohttps://www.acupuncture.org.uk/a-to-z-of-conditions/a-to-z-of-conditions/1815-acupuncture-and-hypertension.html

Palliative carePalliative care

Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes ... Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 2010; May 30. ... and that its anti-nociceptive actions required adenosine A1 receptor expression. ... Increasing the release of adenosine, which has antinociceptive properties (Goldman 2010). *Improving muscle stiffness and joint ...
more infohttps://www.acupuncture.org.uk/a-to-z-of-conditions/a-to-z-of-conditions/palliative-care.html

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Adenosine A1 Receptor Agonists. Not Available. 1. 0. Details. Adenosine A1 Receptor Antagonists. Compounds that bind to and ... Adenosine A2 Receptor Agonists. Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.. 4. 3. Details. ... Adenosine A2 Receptor Antagonists. Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.. 4. ... Adenosine. A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivativ... more. 11. 99. Details. ...
more infohttps://www.drugbank.ca/categories?page=4

Effects of caffeine on learning and memory in rats tested in the Morris water mazeEffects of caffeine on learning and memory in rats tested in the Morris water maze

Von Lubitz DK, Paul IA, Bartus RT & Jacobson KA (1993). Effects of chronic administration of adenosine A1 receptor agonist and ... They argue that adenosine A1 receptor agonists, like N6-(R-phenylisopropyl)adenosine (12) or N6-cyclopentyladenosine (33), do ... Adenosine A1 receptors are expressed densely in the cerebral cortex and hippocampus (27,28). Activation of adenosine A1 ... Cloning and expression of an A1 adenosine receptor from rat brain. Molecular Pharmacology, 40: 1-7. [ Links ]. 29. Briley M ( ...
more infohttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002001000013&lng=en&nrm=iso&tlng=en

World Journal of Gastroenterology - Baishideng Publishing GroupWorld Journal of Gastroenterology - Baishideng Publishing Group

Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat ...
more infohttps://www.wjgnet.com/1007-9327/journal/v13/i4/index.htm

PL2807178T3 - Anhydrous polymorphs of (2r,3s,4r,5r)-5-(6-(cyclopentylamino)-9h-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl) }...PL2807178T3 - Anhydrous polymorphs of (2r,3s,4r,5r)-5-(6-(cyclopentylamino)-9h-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl) }...

Method for producing A1 adenosine receptor agonist US20090220516A1 (en) 2005-06-22. 2009-09-03. Alan Laties. Neuroprotection of ... Partial and full agonists A1 adenosine receptors WO2003013683A1 (en) 2001-08-08. 2003-02-20. Brown University Research ... A3 adenosine receptor agonists US5589467A (en) 1993-09-17. 1996-12-31. Novo Nordisk A/S. 2,5,N6-trisubstituted adenosine ... Combination compositions of adenosine A1 agonists and non-selective beta-adrenergic receptor blockers for reducing intraocular ...
more infohttps://patents.google.com/patent/PL2807178T3/en

Adenosine-induced K+ current in Xenopus oocyte and the role of adenosine 3,5-monophosphate. - Semantic ScholarAdenosine-induced K+ current in Xenopus oocyte and the role of adenosine 3',5'-monophosphate. - Semantic Scholar

The adenosine response is a late long-lasting outward K+ current (H current), mediated by the Ra purine receptor subtype. The ... The converse inhibition of a cyclic AMP response by an earlier adenosine response is also observed but at very high ... It is proposed that the adenosine-evoked K+ outward current is mediated by a rise in intracellular cAMP. ... concentrations of adenosine (greater than 0.6 mM). It was shown by radioimmunoassay that extracellular adenosine increases the ...
more infohttps://www.semanticscholar.org/paper/Adenosine-induced-K%2B-current-in-Xenopus-oocyte-and-Lotan-Dascal/9579d3a28effad495e21a4fb1530cae11cb7060c

Studien zum Thema Wirkmechanismus der Akupunktur › OGKA - Österreichische Gesellschaft für Kontrollierte Akupunktur und...Studien zum Thema Wirkmechanismus der Akupunktur › OGKA - Österreichische Gesellschaft für Kontrollierte Akupunktur und...

Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes ... which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception ... Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. ABSTRACT Acupuncture is an invasive procedure ... was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. ...
more infohttps://ogka.at/studien/wirkmechanismus-der-akupunktur/
  • 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)
  • If subclasses of A 1 AdoR can be shown to be present in adipocytes, then each subclass is potentially an individual drug target of a selective agonist. (aspetjournals.org)
  • 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)
  • Voltage clamp technique was used in Xenopus laevis oocytes in order to study and compare membrane currents evoked by extracellularly applied adenosine (0.1-10 microM) and intracellularly injected cyclic AMP (0.15-10 microM). (semanticscholar.org)
  • The role of the A1 AR in modulating inflammation, necrosis, and apoptosis in the kidney after IR renal injury was further characterized. (elsevier.com)
  • In conclusion, it was demonstrated that endogenous and exogenous preischemic activation of the A1 AR protects against IR injury in vivo, through mechanisms that reduce inflammation, necrosis, and apoptosis. (elsevier.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)
  • suggests the possibility that there are subclasses of these receptors-possibly in the same cell-with inherently different activities and/or coupling to different signaling systems, either in the absence or presence of an agonist. (aspetjournals.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)
  • C57BL/6 mice that had been pretreated with the A 1 AR agonist demonstrated significantly improved renal function and reduced expression of inflammatory markers, necrosis, and apoptosis 24 h after IR injury. (elsevier.com)
  • In contrast, C57BL/6 mice that had been pretreated with the A1 AR antagonist demonstrated significantly worsened renal function and increased expression of inflammatory markers, necrosis, and apoptosis. (elsevier.com)
  • Rat epididymal adipocyte A 1 AdoR had similar affinities for the antagonist 8-cyclopentyl-1,3-dipropylxanthine in the presence of three dissimilar A AdoR agonists (2-chloro- N 6 -cyclopentyladenosine, N 6 -sulfophenyladenosine, and N -5′ -ethylcarboxamidoadenosine) as determined by Schild analysis. (aspetjournals.org)
  • 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)
  • 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)