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)
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Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in...
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 ...
"Repeated treatment with adenosine A1 receptor agonist and antagonist modifies the anticonvulsant properties of CPPene". ... is a drug which acts as a potent and selective antagonist for the adenosine A1 receptor. It has high selectivity for A1 over ... "Potent adenosine receptor antagonists that are selective for the A1 receptor subtype". Molecular Pharmacology. 31 (3): 247-52. ... It has been used to study the function of the adenosine A1 receptor in animals, which has been found to be involved in several ...
2-Chloro-N6-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor. It is similar to N6- ... a high affinity agonist radioligand for A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 340: 679-683. ...
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 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 ...
... an adenosine A1 receptor agonist Cyclophosphamide Cyclopropane fatty acid, a component of some rare fats Cation:Proton ...
"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 ...
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors ... A1 receptors are paired with the G-proteins of Gi-1, Gi-2, Gi-3, Go1, and Go2. The g-proteins of A1 receptors continue to ... Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease ...
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... A1 receptors are also present in smooth muscle throughout the vascular system. The adenosine A1 receptor has been found to be ... "Adenosine Receptors: A1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
... an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist". Br J Pharmacol. 170 (6): 1167- ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ...
... 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 ...
"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 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 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 ...
"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 ...
... 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 ...
"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. ...
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- ...
... 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 ...
"The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia.". J. Biol. ... 2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system.". J. Comp ... alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting ... Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479-92. ...
The other three adenosine receptors are involved in bone formation. In Alzheimer's disease (AD), the expression of A1 and A2A ... Cerqueira, Manuel D (July 2004). "The future of pharmacologic stress: selective a2a adenosine receptor agonists". The American ... In the airways of patients with asthma, the expression of adenosine receptors is upregulated. Adenosine receptors affect ... the expression of adenosine receptors on the neutrophil, and the affinity of these receptors for adenosine. Micromolar ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... highly potent 5-HT1D receptor agonist.". Journal of medicinal chemistry 42 (3): 526-31. PMID 9986723. doi:10.1021/jm9805945. ... 5-HT1D receptor (5-hidroksitriptaminski (serotoninski) receptor 1D, HTR1D) je 5-HT receptor. On je kodiran istoimenim genom.[1] ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • ...
... 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 ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... 1999). „Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor.". FASEB J. 12 (15): ... Gao ZG, Jacobson KA (2007). „Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs. 12 (3): 479-92. PMID ... Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
... 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 ...
腺苷酸（英语：Adenosine receptor） (A1, A2A, A2B, A3) · P2Y（英语：P2Y receptor） (1（英语：P2RY1）, 2（英语：P2RY2）, 4（英语：P2RY4）, 5（英语：LPAR6）, 6（英语： ... SL65.0155（英语：SL65.0155） - partial agonist. *CJ-033,466（英语：CJ-033,466） - partial agonist ... 乙酰胆碱 (M1, M2, M3, M4, M5) · 多巴胺（英语：Dopamine receptor） (D1, D2, D3, D4, D5) · 组织胺（英语：Histamine receptor） (H1, H2, H3, H4) · 褪黑素（ ... α1（英语：Alpha-1 adrenergic receptor） (A, B, D) · α2（英语：Alpha-2 adrenergic receptor） (A, B, C) · β1 · β2
MilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA 25mg:LifeMilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA 25mg Life Sciences:Protein Biology:Protein Extraction and ... MilliporeSigma Calbiochem Adenosine A1 Receptor Agonist I, CPA A potent and selective agonist of adenosine A1 receptor (A1R) (K ... A potent and selective agonist of adenosine A1 receptor (A1R) (Ki = 2.3 nM, 790 nM, 18.6µM, 43nM for human A1, A2A, A2B, and A3 ...
N6-substituted adenosines are full agonists at A1R and activate this receptor selectively over the other adenosine receptor ... Novel Irreversible Agonists Acting at the A1 Adenosine Receptor, Journal of Medicinal Chemistry, 2016, 59, 24, 11182. CrossRef ... and Biological Evaluation of Adenosines with Heterobicyclic and Polycyclic N6-Substituents as Adenosine A1 Receptor Agonists. ... The adenosine A1 receptor (A1R) affinity and potency of these compounds was initially assessed using competitive binding assays ...
Use of 11C-MPDX and PET to study adenosine A1 receptor occupancy by nonradioactive agonists and antagonists - Research database...Use of 11C-MPDX and PET to study adenosine A1 receptor occupancy by nonradioactive agonists and antagonists. Paul, S., Khanapur ... adenosine, adenosine A1 receptor, N-6-cyclopentyladenosine, caffeine, brain, positron emission tomography, PET ... BACKGROUND: Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8- ... PET imaging of adenosine A(1) receptor occupancy. Paul, S., Khanapur, S., Elsinga, P. H., Ishiwata, K., Meerlo, P., Dierckx, R. ...
Optimization of thermolytic response to A1 adenosine receptor agonists in rats | 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 ...
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 ...
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, ...
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 ...
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 ...
Medicinal Chemistry and Therapeutic Potential of Agonists, Antagonists and Allosteric Modulators of A1 Adenosine Receptor:...Keywords:A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR ... Keywords: A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 ... A1 adenosine receptor agonists, antagonists, and allosteric modulators. In: ed, The Adenosine Receptors Springer. 2018; pp. 59- ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ...
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ... Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
title = "Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased ... T1 - Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ... Capadenoson, a clinically trialed partial adenosine A1 receptor agonist, can stimulate adenosine A2B receptor biased agonism. ...
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 ...
Patent US7763635 - Once daily dosage forms of trospium - Google PatentsOrally active a1 adenosine receptor agonists. US20020110593. Jun 4, 1999. Aug 15, 2002. Adel Penhasi. Delayed total release two ... Prodrugs for oxadiazole muscarinic agonists. US5273760. Dec 24, 1991. Dec 28, 1993. Euroceltigue, S.A.. Stabilized controlled ...
Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ... Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ... Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ... T1 - Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl ...
COMPOSITIONS AND METHODS FOR MODULATING AUTOPHAGY - SAN DIEGO STATE UNIVERSITY (SDSU) FOUNDATIONWe 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, ...
![Figler H[au] - PubMed - NCBI](data:image/png;base64,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)
Figler H[au] - PubMed - NCBIDual acting antioxidant A1 adenosine receptor agonists.. Gregg A, Bottle SE, Devine SM, Figler H, Linden J, White P, Pouton CW ... 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 adenosine receptor agonist allosteric enhancers having improved potency. ... Allosteric enhancers of A1 adenosine receptors increase receptor-G protein coupling and counteract Guanine nucleotide effects ... Synthesis and evaluation of new N6-substituted adenosine-5-N-methylcarboxamides as A3 adenosine receptor agonists. ...
adenosine A1 receptor agonist An agonist at the A. 1. receptor.. Application(s):. nutraceutical A product in capsule, tablet or ... adenosine 5-monophosphate (CHEBI:16027) has role adenosine A1 receptor agonist (CHEBI:65057) adenosine 5-monophosphate (CHEBI ... adenosine 5-monophosphate (CHEBI:16027) is a adenosine 5-phosphate (CHEBI:37096) adenosine 5-monophosphate (CHEBI:16027) is ... adenosine 5-monophosphate(1+) (CHEBI:40721) is conjugate acid of adenosine 5-monophosphate (CHEBI:16027). adenosine 5- ...
Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist | PNAS1991) Activity of N6-substituted 2-chloroadenosines at A1 and A2 adenosine receptors. J Med Chem 34(12):3388-3390. ... 2007) New fluorescent adenosine A1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains ... 2010) A novel highly selective adenosine A1 receptor agonist VCP28 reduces ischemia injury in a cardiac cell line and ischemia- ... 2012) The role of the second and third extracellular loops of the adenosine A1 receptor in activation and allosteric modulation ...
Structure-kinetics relationships of Capadenoson derivatives as adenosine A1 receptor agonists.. Louvel J, Guo D, Soethoudt M, ... Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A3 Receptor. ... A covalent antagonist for the human adenosine A2A receptor.. Yang X, Dong G, Michiels TJM, Lenselink EB, Heitman L, Louvel J, ... Sodium ion binding pocket mutations and adenosine A2A receptor function.. Massink A, Gutiérrez-de-Terán H, Lenselink EB, Ortiz ...
Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A1 Receptor Antagonists (3) • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. MeSH ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ...
Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and...Selectivity against receptors was tested on the MDS "Profiling" panel, including adenosine A1; adrenergic (α1 and α2 ... nonselective and β1 and β2); calcium channel type L; dopamine D1 and D2; estrogen α; GABAA (agonist site and sodium channel); ... including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor (6,7). Tyrosine- ... insulin receptor substrate 1; oGTT, oral glucose tolerance test; PI, phosphatidylinositol; PKC, protein kinase C; RTK, receptor ...
"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 ...
... 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 ...
Pharmacology of Restless Legs Syndrome (RLS), Volume 84 - 1st Edition3. The heterotetrameric structure of the adenosine A1-dopamine D1 receptor complex: Pharmacological implication for restless ... 2. D3 receptor agonist efficacy in restless legs syndrome. Francesca Casoni, Andrea Galbiati and Luigi Ferini-Strambi. ... Rationale for the use of inhibitors of adenosine transport. Sergi Ferré, César Quiroz, William Rea, Xavier Guitart and Diego ... 4. D3 and D1 receptors: The Yin and Yang in the treatment of restless legs syndrome with dopaminergics. Stefan Clemens and Imad ...
... an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist". Br J Pharmacol. 170 (6): 1167- ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ...
AntagonistAntagonistsLigandsInhibitionAbstractNECAAffinitySubtypes of adenosine receptorsDerivativesPharmacologicalPharmacologyRadioligandGPCRsStimulationProteinsNucleosideCaffeineModulationModulatorsCCPAEffect of adenosineRatsGPCRAdministration of adenosineInhibitsNeuropathic painPhysiologicalMiceKinaseFull agonist1998Activation of adenosine receptorsDrugs that inhibit ADENOSINE DEAMINASEPurinePartial agonistInflammationExtracellular adenosineMediateSubtypeMyocardialAdenylyl cyclase activityBlockadeEffectsNicotinic AcetylchoInteractionsAnaloguesInhibitorsCardioprotectiveSelectivityAllosteric ModulatorCyclopentyladenosineProtein-coupled receptor
- CONCLUSION: Small-animal PET with (11)C-MPDX can be used to assess antagonist but not agonist binding at A1Rs. (rug.nl)
- 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)
- 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)
- A thermodynamic analysis of the binding of a full agonist (N6-cyclopentyladenosine), a partial agonist (8-butylamino-N6-cyclopentyladenosine) and an antagonist (8-cyclopentyltheophylline) to human wild-type and mutant (mutation of a threonine (Thr) to an alanine (Ala) residue at position 277) adenosine A1 receptors expressed on Chinese hamster ovary (CHO) cells, and to rat brain adenosine A1 receptors was undertaken. (garvan.org.au)
- Affinity constants were obtained from inhibition assays on membrane preparations of rat brain and CHO cells by use of the antagonist [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) as selective adenosine A1 receptor radioligand. (garvan.org.au)
- As for rat brain receptors, full agonist binding was totally entropy driven, whereas antagonist binding was essentially enthalpy driven. (garvan.org.au)
- Addition of a 120-fold molar excess of a purified bovine brain G-protein preparation (Go,i a mixture of Go and Gi, containing predominantly Go) decreases the Bmax of the binding of the antagonist radioligand [3H]XAC to the receptor. (biochemj.org)
- The ability of Go,i to enhance agonist binding and decrease antagonist binding is concentration-dependent, with a half-maximal effect occurring at approximately 10-fold molar excess of G-proteins over A1-adenosine receptors. (biochemj.org)
- This rate is further enhanced if the receptor is activated by the agonist (-)(R)-N6-phenylisopropyladenosine, whereas the antagonist XAC decreases the association rate of GTP[35S] to levels observed in the absence of receptor. (biochemj.org)
- These results show (1) that detergent removal is not a prerequisite for the observation of coupling between the A1-adenosine receptor and Go,i, and (2) that the regulatory effect of G-proteins on antagonist binding to the A1-adenosine receptor can be reconstituted by using purified components. (biochemj.org)
- Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A 1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. (elsevier.com)
- Antagonist exposure (1) increased the density of A 1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. (elsevier.com)
- On page 747, the word "antagonist" was incorrectly published instead of "agonist. (wiley.com)
- These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. (jneurosci.org)
- Caffeine, the adenosine A1 antagonist 8-cyclopentyltheophylline (CPT), and the adenosine A2A antagonist 5-amino-7-(2-phenylethyl)2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261) were administered intraperitoneally in all experiments. (jneurosci.org)
- The role of the A1 receptor and adenosine was also confirmed by showing that high-frequency stimulation failed to reduce evoked excitatory postsynaptic potentials (eEPSPs) in the presence of an A1 receptor antagonist or an inhibitor of ectoATPase activity. (sciencemag.org)
- In competition with antagonist radioligand biphasic curves were observed for agonists. (biomedsearch.com)
- We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. (scielo.br)
- Aki Y, Tomohiro A, Nishiyama A et al (1997) Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs. (springer.com)
- 1. A method of enhancing an immune response in a host, comprising administering to the host an A.sub.2a receptor antagonist in combination or alternation with a checkpoint inhibitor. (patents.com)
- However, a clear picture of how these receptors bind their various agonist and antagonist ligands to transduce signals across the cell membrane has yet to emerge because of a lack of definitive structural evidence in the field. (aspetjournals.org)
- The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. (wikipathways.org)
- NECA was chosen for the study because caffeine is a nonselective adenosine receptor antagonist, and it is not known which of the four subtypes of adenosine receptors may be involved in an effect of caffeine on fatigue. (innovations-report.com)
- To ascertain receptor mechanism, Flögel and colleagues used only one A2A antagonist (KW-6002) at a single concentration in vivo (delivered continuously for 1-2 weeks using an osmotic minipump). (painresearchforum.org)
- Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. (ovid.com)
- The effects of adenosine, CPA and ATP were inhibited by DPCPX, a selective adenosine A1 receptor antagonist. (ovid.com)
- In the presence of the GABA(A) receptor antagonist bicuculline, ANOs were transformed to epileptiform discharges. (inserm.fr)
- 5. In the presence of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the anoxia induced an epileptiform activity and no ANOs were observed. (inserm.fr)
- C57BL/6 mice were subjected to 30 min of renal ischemia, with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine or 2-chlorocyclopentyladenosine (selective A 1 AR antagonist and agonist, respectively). (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)
- Pre-treatment of the omentum with the A 1 /A 2 receptor antagonist 8-phenyltheophylline or with the more specific A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reduced agonist-induced degranulation. (hindawi.com)
- Theophylline** Theophylline is an adenosine receptor antagonist. (rutgers.edu)
- The selective cannabinoid 1 receptor (CB1R) antagonist AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] prevented the response, demonstrating CB1R mediation of 2-AG-induced coupling. (420magazine.com)
- Here we investigated whether A1R occupancy by nonradioactive agonists and antagonists can be assessed with this technique. (rug.nl)
- Agonists and antagonists may bind to different sites on the A1R protein having allosteric interactions. (rug.nl)
- This review provides an overview of the medicinal chemistry and therapeutic potential of various agonists/partial agonists, antagonists and allosteric modulators of A1 AR, with a particular emphasis on their current status and future perspectives in clinical settings. (eurekaselect.com)
- A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR. (eurekaselect.com)
- A1 adenosine receptor agonists, antagonists, and allosteric modulators. (eurekaselect.com)
- Primary cultures of cerebellar granule cells were exposed chronically to A 1 adenosine receptor agonists and antagonists. (elsevier.com)
- The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A 1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. (elsevier.com)
- Hettinger-Smith, BD, Leid, M & Murray, TF 1996, ' Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl cyclase system in cerebellar granule cells ', Journal of Neurochemistry , vol. 67, no. 5, pp. 1921-1930. (elsevier.com)
- 3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists. (nih.gov)
- 2-aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists. (nih.gov)
- Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5. (nih.gov)
- Structure-Affinity Relationships and Structure-Kinetic Relationships of 1,2-Diarylimidazol-4-carboxamide Derivatives as Human Cannabinoid 1 Receptor Antagonists. (nih.gov)
- Kinetics of human cannabinoid 1 (CB1) receptor antagonists: Structure-kinetics relationships (SKR) and implications for insurmountable antagonism. (nih.gov)
- The adenosine receptors are commonly known for their antagonists caffeine and theophylline , whose action on the receptors produces the stimulating effects of coffee , tea and chocolate . (wikipedia.org)
- Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A 1 and A 2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. (wikipedia.org)
- Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. (wikipedia.org)
- Specific A 1 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3- dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine ( CCPA ). (wikipedia.org)
- Adenosine receptors: development of selective agonists and antagonists. (biomedsearch.com)
- The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. (patents.com)
- Carprolactams as Potent CGRP Receptor Antagonists for the Treament of Migraine", Bioorg Med. (patents.com)
- Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice. (semanticscholar.org)
- Described are uses of A.sub.2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses. (patents.com)
- A.sub.2a receptor antagonists in particular are provided to enhance immune responses by reducing T-cell mediated tolerance to antigenic stimuli and agonists are provided to enhance effectiveness of immunosuppressive agents. (patents.com)
- This application relates to uses of A.sub.2a adenosine receptor agonists and antagonists to modulate T-cell mediated tolerance to antigenic stimuli. (patents.com)
- Several synthetic compounds have been shown to act on neurons specific to the preBötC, most being selective agonists or antagonists to receptor subtypes on neurons in the vicinity. (wikipedia.org)
- In addition, the hydroxyl moiety at position 277 in the hA 1 AR was shown to be of particular importance for high-affinity 5′-substituted agonist (NECA) binding but not for the binding of antagonists ( Townsend-Nicholson and Schofield, 1994 ). (aspetjournals.org)
- Our overall goals are to design, chemically synthesize, and characterize pharmacologically new agonists and antagonists for the four subtypes of adenosine receptors (ARs) and eight subtypes of P2Y receptors and to explore their potential for treating human disease conditions. (nih.gov)
- I am a medicinal chemist with interests in the structure and pharmacology of receptors and in developing drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
- Recent accomplishments include the design and synthesis of the highly potent and selective A3 adenosine receptor agonists and antagonists, using a combination of library screening and optimization of known adenosine receptor ligands. (nih.gov)
- We have synthesized the first P2Y1 receptor-selective antagonists through functionalization of adenine nucleotides. (nih.gov)
- The antagonists were optimized with the aid of receptor homology modeling. (nih.gov)
- The concepts describing ligand interactions with receptors have also been refined from the simple binary concept of competitive agonists and antagonists to partial agonists, allosteric modulators and inverse agonists. (currentprotocols.com)
- Update on novel purinergic P2X3 and P2X2/3 receptor antagonists and their potential therapeutic applications. (wikipathways.org)
- Potent adenosine receptor antagonists that are selective for the A1 receptor subtype. (wikipathways.org)
- Behavioral effects of A1- and A2-selective adenosine agonists and antagonists: evidence for synergism and antagonism. (nih.gov)
- Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. (ovid.com)
- The selective adenosine A2 and A3 receptors antagonists did not alter the chronotropic response of adenosine. (ovid.com)
- 4. ANOs were prevented by tetrodotoxin and glutamate receptor antagonists CNQX and APV, and were slowed down by the allosteric GABA(A) receptor modulator diazepam. (inserm.fr)
- To investigate the nature of the receptors involved in adenosine-induced mast cell degranulation in the rat isolated omentum we have used adenosine analogues with varying specificities as activators of the A 1 , A 2 and A 3 receptors, and antagonists with differing specificities for A 1 and A 2 receptors. (hindawi.com)
- It was concluded that rat epididymal adipocyte A 1 AdoR are a homogeneous receptor population with regard to affinities for ligands and that CVT-3619 is a partial agonist with selectivity for A 1 AdoR and inhibition of lipolysis. (aspetjournals.org)
- Multivalent site-specific phage modification enhances the binding affinity of receptor ligands. (nih.gov)
- We validate that the interaction of VCP746 with the A 1 AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A 1 AR ligands. (pnas.org)
- Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects. (pnas.org)
- Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A 3 Receptor. (nih.gov)
- Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
- These cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands. (biomedsearch.com)
- The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). (springer.com)
- Extensive structure-activity relationships exist for ligands that were engineered to be selective for the various subtypes of the receptor ( Linden, 1991 ). (aspetjournals.org)
- Novel ligands (small molecules) for these receptors are developed using classical synthetic approaches and also by semirational methods based on molecular modeling and template design. (nih.gov)
- These can be quantified by determination of key parameters (left) and used to construct "Webs of Bias", an example of which is shown on the right for signalling of three different ligands at the adenosine A1 receptor. (monash.edu)
- Klotz (2000) Adenosine receptors and their ligands. (tocris.com)
- 3 PDGF ligands, established as potent mitogens, chemotactic agents, and inducers of matrix synthesis, produce effects by dimerization and activation of PDGF-receptor (PDGFr) subunits. (ahajournals.org)
- The expression of both ligands and receptor in regions of vascular repair provides evidence that autocrine/paracrine loops promoting PDGF-driven cellular activities, occur in human restenotic lesions. (ahajournals.org)
- Functional selectivity of an A 1 AdoR agonist for inhibition of lipolysis could also be achieved if adipocyte A 1 AdoR could be distinguished pharmacologically from A 1 AdoR in other tissues. (aspetjournals.org)
- Insulin indirectly relieves GS inhibition ( 4 , 5 ) through a signaling cascade beginning with phosphorylation of substrates, including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor ( 6 , 7 ). (diabetesjournals.org)
- Adenosine was detected in the thalamic slices with an amperometric biosensor, and production by ectoATPases was confirmed by pharmacological inhibition. (sciencemag.org)
- Aldose reductase inhibition alone or combined with an adenosine A(3) agonist reduces ischemic myocardial injury. (semanticscholar.org)
- This study investigated whether aldose reductase (AR) inhibition with zopolrestat, either alone or in combination with an adenosine A(3)-receptor agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion. (semanticscholar.org)
- Inhibition of rat ventricular automaticity by adenosine. (semanticscholar.org)
- Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
- Agonist activity at human Adenosine A1 receptor transfected in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production after 30 m. (bindingdb.org)
- To avoid these undesirable effects, indirect approaches, such as allosteric adenosine receptor modulation or inhibition of adenosine kinase 9,10 or adenosine deaminase, 11 have been examined and show antinociceptive effects in neuropathic rats. (asahq.org)
- Finally, the pharmacologic inhibition of enzymes involved in adenosine degradation potentiate both the acupuncture-elicited increase in adenosine, as well as its antinociceptive effect. (chiroaccess.com)
- As a result, stimulation of A1 and A3 subtypes in general results in neurotransmission through the inhibition of adenylate cyclase and phospholipase C , whereas stimulation of the A2 subtypes leads to enhanced neurotransmission. (axonmedchem.com)
- Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. (wikipathways.org)
- 1999) 5HT1B receptor-mediated presynaptic inhibition of retinal input to the suprachiasmatic nucleus. (uh.edu)
- Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. (ahajournals.org)
- the PDGFr was purified from human VSMC and the final ATP concentration was 20 μmol/L. Inhibition of PDGFr-dependent activities, including in situ receptor autophosphorylation, mitogenesis, cell number, and viability were as described. (ahajournals.org)
- abstract = "Adenosine released into the extracellular space by immunologic and nonimmunologic stimuli has been shown to regulate various immune functions. (utmb.edu)
- Relative to the non-selective adenosine receptor agonist NECA, capadenoson was a biased A 2B AR agonist with a preference for cAMP signal transduction over other downstream mediators in cells with recombinant and endogenous A 2B AR expression. (monash.edu)
- For A2A adenosine receptors CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadeno sine) and N-ethylcarboxamidoadenosine (NECA) were found to be the most potent agonists followed by R- and S-PIA with minor stereoselectivity. (biomedsearch.com)
- NECA was the most potent agonist with an EC50-value of 2.3 microM whereas all other compounds tested were active at concentrations in the high micromolar range. (biomedsearch.com)
- The A3 receptor was characterized utilizing the nonselective agonist [3H]NECA. (biomedsearch.com)
- To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
- Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (physiology.org)
- Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (physiology.org)
- The researchers' hypothesis is the foundation of a new study to determine the effects of intracerebroventricular injection of caffeine and the adenosine A1 and A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on treadmill run time to fatigue in rats. (innovations-report.com)
- The drugs chosen were, R-phenylisopropyl-adenosine (R-PIA) with high affinity for the A1 receptor, N-ethylcarboxamide-adenosine (NECA) with almost equal affinity for the A1 and A2 receptor and 2-(2-aminoethylamino)-carbonylethylphenylethylamino-adenosin e (APEC) with high affinity for the A2 receptor. (nih.gov)
- The adenosine A 1 receptor (A 1 R) affinity and potency of these compounds was initially assessed using competitive binding assays and cyclic adenosine monophosphate (cAMP) accumulation assays in DDT 1 MF-2 cells. (wiley.com)
- The thermodynamic parameters deltaGo (standard free energy), deltaHo (standard enthalpy) and deltaSo (standard entropy) of the binding equilibrium to rat brain receptors were determined by means of affinity measurements carried out at four different temperatures (0, 10, 20 and 25 degrees) and van't Hoff plots. (garvan.org.au)
- As for human receptors, full agonist affinity was highly dependent on the presence of Thr277. (garvan.org.au)
- Moreover, affinity to both wild-type and mutant receptors was enhanced by temperature increase, suggesting a totally entropy-driven binding. (garvan.org.au)
- The bovine brain A1-adenosine receptor was purified 8000-fold by affinity chromatography on xanthine-amine-congener (XAC)-Sepharose. (biochemj.org)
- In the presence of Go,i, about 20 and 40% of the receptors display guanine-nucleotide-sensitive high-affinity binding of the agonist radioligand (-)-N6-3-([125I]iodo-4-hydroxyphenylisopropyl)adenosine after reconstitution into lipid vesicles and in detergent solution, respectively. (biochemj.org)
- The A1 subtype showed the typical pharmacological profile with 2-chloro-N6-cyclopentyladenosine (CCPA) as the agonist with the highest affinity and a marked stereoselectivity for the N6-phenylisopropyladenosine (PIA) diastereomers. (biomedsearch.com)
- In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. (biomedsearch.com)
- The notion of xanthine-insensitivity of the A3 receptor should be dropped at least for the human receptor as xanthines with submicromolar affinity were found. (biomedsearch.com)
- Regadenoson is an selective low-affinity (Ki= 1.3 µM) A2A receptor agonist that mimics the effects of adenosine in causing coronary vasodilatation and increasing myocardial blood flow. (drugbank.ca)
- Furthermore, it has negligible affinity to A2B and A3 adenosine receptors. (drugbank.ca)
- Stimulation of adenosine A1 receptors increases the affinity of dinucleotide receptors by five orders of magnitude, from 30 μM to 680 pM for control and in the presence of A1 agonist, respectively. (mendeley.com)
- 2-Chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA)--a high affinity agonist radioligand for A1 adenosine receptors. (wikipathways.org)
- Four subtypes of adenosine receptors (ARs) have been identified among vertebrates so far ( A1 , A2A , A2B and A3 ). (axonmedchem.com)
- It is concluded that Thr277 contributes only to the binding of adenosine derivatives and that its role changes drastically with the receptor conformation and with the type of agonist (full or partial) interacting with the adenosine A1 receptors. (garvan.org.au)
- Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2. (nih.gov)
- Derivatives of adenosine are widely found in nature and play an important role in biochemical processes, such as energy transfer-as adenosine triphosphate (ATP) and adenosine diphosphate (ADP)-as well as in signal transduction as cyclic adenosine monophosphate (cAMP). (wikipedia.org)
- CPA is widely used in scientific research into the adenosine receptors and has been used to derive a large family of derivatives. (wikipedia.org)
- Both adenosine and xanthine derivatives bind competitively to A-1 and A-2 adenosine receptors. (patentgenius.com)
- The N6-benzyl substituted derivatives of adenosine-5'-N-methyluronamide (MECA) turned out to be the most potent agonists. (biomedsearch.com)
- Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy In: ed Protein Reviews. (eurekaselect.com)
- The adenosine A 2B receptor (A 2B AR) has been identified as an important therapeutic target in cardiovascular disease, however in vitro and in vivo targeting has been limited by the paucity of pharmacological tools, particularly potent agonists. (monash.edu)
- In this study all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). (biomedsearch.com)
- Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. (biomedsearch.com)
- The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. (biomedsearch.com)
- Relative importance of adenosine A1 and A3 receptors in mediating physiological or pharmacological protection from ischemic myocardial injury in the rabbit heart. (semanticscholar.org)
- We are interested in correlating structure of receptors and small molecular drugs with pharmacological properties. (nih.gov)
- Substances developed as potent and selective agents acting through adenosine and P2 receptors have proven useful as pharmacological probes and have potential for treating diseases of the central nervous system, immune system, and cardiovascular system. (nih.gov)
- Boison D, Stewart K-A (2009) Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation. (springer.com)
- Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: the state of the art. (eurekaselect.com)
- Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
- In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. (biomedsearch.com)
- Monopoli et al (1994) Pharmacology of the highly selective A 1 adenosine receptor agonist 2-chloro- N 6 -cyclopentyladenosine. (tocris.com)
- BACKGROUND: Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX) and PET. (rug.nl)
- Adenosine is a purine nucleoside, responsible for the regulation of a wide range of physiological and pathophysiological conditions by binding with four G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B and A3 adenosine receptors (ARs). (eurekaselect.com)
- The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). (pnas.org)
- G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins and tractable drug targets ( 1 , 2 ). (pnas.org)
- Intracellular Receptor Modulation: Novel Approach to Target GPCRs. (nih.gov)
- Here, we overexpressed mouse DGK η in human embryonic kidney 293 cells to examine substrate specificity and signaling downstream of endogenous G protein-coupled receptors (GPCRs). (aspetjournals.org)
- Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol. (frontiersin.org)
- Receptors are computer-modeled by homology to GPCRs of known structure, and the models for ligand recognition are tested and refined using site-directed mutagenesis of the receptor proteins. (nih.gov)
- Recently, the involvement of extracellular loops of GPCRs have been implicated in the receptor binding of small molecules. (nih.gov)
- G protein-coupled receptors (GPCRs) represent the largest family of receptor proteins encoded by the human genome and the biggest class of current drug targets. (monash.edu)
- The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses. (sciencemag.org)
- G protein-coupled receptors (GPCRs) are a major target for hormones, neurotransmitters, and cytokines. (sciencemag.org)
- Ubiquitously expressed arrestin 2 and 3 (β arrestin 1 and 2) associate with agonist-evoked conformations of GPCRs that are phosphorylated by GRKs to mediate desensitization ( 3 , 4 ) and endocytosis via clathrin-coated pits ( 5 ). (sciencemag.org)
- Spinophilin is a ubiquitously expressed protein containing an F-actin-binding domain, a phosphatase 1 (PP1) binding and regulatory domain, a protein-interaction PDZ domain, and C-terminal coiled-coil domains ( 9 , 10 ), and interacts with at least two subfamilies of GPCRs, the α 2 AR subtypes ( 11 ) and the D2 dopamine receptor ( 12 ). (sciencemag.org)
- Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. (nih.gov)
- provide evidence that one mechanism by which DBS reduces tremor is through stimulation of nonsynaptic release of adenosine triphosphate (ATP). (sciencemag.org)
- The release of ATP was deemed to be nonsynaptic, because it did not require calcium and removal of extracellular calcium increased the accumulation of adenosine in response to high-frequency stimulation. (sciencemag.org)
- Application of adenosine or an A1 receptor agonist reduced eEPSP amplitude in the absence of high-frequency stimulation. (sciencemag.org)
- In slices from mice deficient for A1 receptors, high-frequency stimulation failed to reduce eEPSP amplitude. (sciencemag.org)
- Deep brain stimulation appears to trigger nonsynaptic release of ATP, which when converted to adenosine contributes to the tremor-reducing effects of this treatment. (sciencemag.org)
- Besides, stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. (axonmedchem.com)
- Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of α 2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. (sciencemag.org)
- Now, a team of researchers from the University of South Carolina has hypothesized that the blockade of adenosine receptors by caffeine may be the most likely mechanism of CNS stimulation and delayed fatigue. (innovations-report.com)
- The haemodynamic effects of adenosine are thought to result in part from a release of mast cell amines via A3 receptor stimulation. (hindawi.com)
- In the rat isolated omental mast cell we conclude that degranulation is an indirect result of A 1 receptor stimulation. (hindawi.com)
- Theophylline-induced respiratory recovery following cervical spinal cord hemisection is augmented by serotonin 2 receptor stimulation. (rutgers.edu)
- The present study was designed to specifically determine if concurrent stimulation of 5-HT2 receptors may enhance motor recovery induced by theophylline alone. (rutgers.edu)
- These results demonstrate that adenosine receptor stimulation differentially modulates the LPS-induced production of IL-10, TNF-α, and NO in vitro and in vivo. (utmb.edu)
- Interactions of purified bovine brain A1-adenosine receptors with G-proteins. (biochemj.org)
- Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
- Adenosine receptors are members of the GPCR superfamily of cell surface receptor proteins. (aspetjournals.org)
- The concepts of the receptor and receptor theory, based on the Law of Mass Action, have undergone continuous refinement as they have been characterized in terms of their molecular structure, association with ancillary proteins (e.g. (currentprotocols.com)
- Expanding horizons for receptors coupled to G proteins: Diversity and disease. (currentprotocols.com)
- 8 9 Additionally, PDGFr activity, as determined by the state of receptor autophosphorylation, increases several days postinjury and persists for several weeks, 10 11 providing a functional link between expression of PDGFr/ligand mRNA 9 and proteins 10 11 and potential biological influence on arterial stenosis. (ahajournals.org)
- Immunofluorescence and in vitro [35S]GTPγS autoradiography of rat tissue sections containing the PBN revealed the presence of cannabinoid receptors and their functional capability to couple to their G-proteins after incubation with the endocannabinoid 2-arachidonoyl glycerol (2-AG). (420magazine.com)
- Adenosine is a purine nucleoside composed of a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond. (wikipedia.org)
- "Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. (tcdb.org)
- In this regard, the level of nucleoside adenosine is increased in individuals with obesity. (elsevier.es)
- Effects of adenosine on tubular transport are most pronounced in the proximal tubule where the nucleoside stimulates NaCl reabsorption in the subnormal concentration range while inhibiting transport at elevated levels. (springer.com)
- Because adenosine production increases in hypoxia, the issue of a role of the nucleoside in the renal injury following ischemia reperfusion has been studied extensively. (springer.com)
- As a breakdown product of ATP, adenosine is an endogenous purine nucleoside that modulates many physiological processes in all cells of the body. (physiology.org)
- The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. (springer.com)
- Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5′-nucleotidase. (springer.com)
- Caffeine keeps you awake by blocking adenosine receptors. (wikipedia.org)
- This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages. (jneurosci.org)
- The main mechanism of action of caffeine in the brain seems to be a nonselective competitive blockade of adenosine receptors, in particular adenosine A1 receptors and A2A receptors ( Daly and Fredholm, 1998 ). (jneurosci.org)
- Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. (semanticscholar.org)
- Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O(2)C) were studied in awake mice lacking one or both of the adenosine A(1) or A(2A) receptors (A(1)R or A(2A)R, respectively) using telemetry and respirometry, before and after caffeine administration. (semanticscholar.org)
- Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade. (semanticscholar.org)
- In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialog. (elsevier.es)
- Among these indirect approaches, allosteric adenosine receptor modulation represents a novel drug development direction to potentiate A1 receptor function and agonist binding via a conformation change. (asahq.org)
- Interaction of [3H]orphanin FQ and 125I‐tyr14‐orphanin FQ with the orphanin FQ receptor: Kinetics and modulation by cations and guanine nucleotides. (currentprotocols.com)
- The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. (deepdyve.com)
- To address this, we utilize mutagenesis, biophysical techniques, x-ray crystallography and cutting edge computational modeling and docking methods to understand receptor dynamics and drug-receptor interactions, especially in the context of allosteric modulators and biased agonists. (monash.edu)
- 2-Chloro-N 6 -cyclopentyladenosine (CCPA), an agonist of A 1 adenosine receptors, at 0.5 mg/kg diminished LPS-induced plasma TNF-α concentrations, but enhanced LPS-induced IL-10 levels only at the highest dose used (2 mg/kg). (utmb.edu)
- Babich V, Vadnagara K, Di Sole F (2015) Dual effect of adenosine a1 receptor activation on renal O2 consumption. (springer.com)
- Changes in tracer uptake after the administration of CPA resembled previously reported changes induced by treatment of rats with ethanol and an adenosine kinase inhibitor (ABT702). (rug.nl)
- These low molecular weight compounds activated glycogen synthase at ∼100 nmol/l in cultured CHO cells transfected with the insulin receptor and in primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. (diabetesjournals.org)
- Importantly, also in response to an adenosine A1 agonist, old rats had less sleep compared with young animals. (wiley.com)
- ASP5854 ameliorated A(2A) agonist 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680)- and haloperidol-induced catalepsy in mice, with the minimum effective doses of 0.32 and 0.1 mg/kg, respectively, and it also improved haloperidol-induced catalepsy in rats at doses higher than 0.1 mg/kg. (curehunter.com)
- 12,13 An adenosine receptor modulator, T62, belonging to a group of thiophene compounds first described a decade ago, 14 has been shown to reduce mechanical allodynia in spinal nerve-injured rats after oral, parenteral, or intrathecal application. (asahq.org)
- Berman RF, Fredholm BB, Aden U, O'Connor WT (2000) Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats. (springer.com)
- Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of Wistar rats? (ovid.com)
- Adenosine A1 receptor activation by adenosine and ATP produces cardiac arrest in the right atrium of Wistar rats predominantly through activation of potassium channels. (ovid.com)
- It was previously demonstrated that preischemic A 1 adenosine receptor (AR) activation protects renal function after ischemia-reperfusion (IR) injury in rats. (elsevier.com)
- The adenosine A 1 GPCR (A 1 AR) is a major therapeutic target for cardioprotection, but current agents acting on the receptor are clinically limited for this indication because of on-target bradycardia as a serious adverse effect. (pnas.org)
- Dysregulation of G protein-coupled receptor (GPCR) activity is involved in the pathology of many psychiatric disorders, including BPD ( Catapano and Manji, 2007 ). (aspetjournals.org)
- Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. (sciencemag.org)
- The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. (wikipedia.org)
- In protocol B, risk zones were similar, but administration of adenosine resulted in significant reductions in infarct size from 59 ± 3% of the area-at-risk in control swine to 46 ± 4% (p = 0.02), and no-reflow from 49 ± 6% of the infarct area to 26 ± 6% (p = 0.03). (onlinejacc.org)
- The aim of the present study was to investigate the effect of peripheral administration of adenosine agonists with different affinities for the A1 and A2 adenosine receptors on a persistent pain stimulus using the formalin test. (nih.gov)
- Their theory is based on the fact that adenosine is produced within the body and inhibits neuronal excitability and synapse transmission. (innovations-report.com)
- Adenosine also inhibits the release of most brain excitatory neurotransmitters, particularly dopamine (DA), and may reduce DA synthesis. (innovations-report.com)
- Rea MA , Pickard GE, (2000) 5-HT1B receptor agonist inhibits light-induced suppression of pineal melatonin production. (uh.edu)
- Emala, Charles W. / A 1 Adenosine Receptor Activation Inhibits Inflammation, Necrosis, and Apoptosis after Renal Ischemia-Reperfusion Injury in Mice . (elsevier.com)
- 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)
- Our results demonstrated an involvement of adenosine A 1 receptor in the amplified nociceptive thresholds and in spinal glial and microglial changes occurred in neuropathic pain, without affecting motor coordination or blood pressure. (mdpi.com)
- Our data suggest a possible use of adenosine A 1 receptor agonist in neuropathic pain symptoms. (mdpi.com)
- Allosteric enhancer of A1 AR is found to be potent for the treatment of neuropathic pain, culminating the side effects related to off-target tissue activation of A1 AR. (eurekaselect.com)
- Among several novel approaches that seem promising in relief of neuropathic pain, adenosine receptor agonists have attracted considerable attention. (asahq.org)
- We recently published in collaboration with Daniela Salvemini of St. Louis University the protective effect of A3 agonists in animal models of neuropathic pain. (nih.gov)
- We have discovered highly specific A3 agonists that reduce neuropathic pain in the mouse and rat and prevent its development. (nih.gov)
- In particular, A1 AR is ubiquitously present, mediating a variety of physiological processes throughout the body, thus represents a promising drug target for the management of various pathological conditions. (eurekaselect.com)
- Adenosine-a physiological or pathophysiological agent? (eurekaselect.com)
- However, A2b and A3 receptors are relatively less active than A1 and A2a receptors under normal physiological conditions. (innovations-report.com)
- Our research unexpectedly suggested that some of the physiological effects of AMP (and AMP analogs) might be due to direct activation of adenosine receptors and independent of ectonucleotidases. (painresearchforum.org)
- The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas , in the lipidic and glycemic metabolism in FVB/N mice. (diabetesjournals.org)
- An adenosine A1 receptor agonist has been shown to depress preBötC rhythmogenesis independent of the neurotransmitters GABA and glycine in in vitro preparations from 0-7 day old mice. (wikipedia.org)
- Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupuncture. (ogka.at)
- All of these effects are obliterated in knockout genetic strains of mice which lack the adenosine A1 receptor. (chiroaccess.com)
- We recently found an A1 adenosine receptor agonist that has antiseizure effects in mice without some of the side effects associated with such agonists in the past. (nih.gov)
- Adenosine, a neuromodulator with anti-pain properties, was released during acupuncture in mice. (thecamreport.com)
- Borowicz KK, Luszczki J, Czuczwar SJ (2002) 2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice. (springer.com)
- Influences of different adenosine receptor subtypes on catalepsy in mice. (nih.gov)
- 2002). 5-HT1B receptor knockout mice exhibit an enhanced response to constant light. (uh.edu)
- One of these AMP analogs was orally active and had A1-dependent antinociceptive effects in mice with minimal to no cardiovascular side effects. (painresearchforum.org)
- 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 this study we report that i.p. pretreatment of mice with CGS-21680 HCl (CGS), a selective agonist of A 2 adenosine receptors, at 0.2 to 2 mg/kg caused an augmentation of plasma IL-10 levels induced by i.p. injection of LPS, but decreased plasma levels of LPS-induced TNF-α. (utmb.edu)
- Since protein kinase C (PKC) can be activated by DAG and promotes receptor desensitization, we also examined functional interactions between PKC and DGK η . (aspetjournals.org)
- Boison D (2008) The adenosine kinase hypothesis of epileptogenesis. (springer.com)
- Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gβγ complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. (sciencemag.org)
- During simulated ischemia, cultured myocytes with enhanced expression of the human A3 receptor and showed significantly higher ATP content, fewer cells killed, and less creatine kinase released into the medium than either control or mock-transfected myocytes. (garvan.org.au)
- Background -Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. (ahajournals.org)
- A partial agonist may either stabilize a less active receptor conformation or activate a smaller portion of a dichotomous receptor population than a full agonist. (aspetjournals.org)
- Many functional studies have described the signaling roles of the different subtypes of adenosine receptor ( Poulsen and Quinn, 1998 ). (aspetjournals.org)
- Franchetti et al (1998) 2'-C-Methyl analogues of selective adenosine receptor agonists: synthesis and binding studies. (tocris.com)
- Weber ET, Gannon RL, Rea MA (1998) Local administration of serotonin agonists blocks light-induced phase advances of the circadian activity rhythm in hamsters. (uh.edu)
- We found that activation of adenosine receptors affected the proliferation of NPCs. (deepdyve.com)
- We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. (physiology.org)
- Baranowski RL, Westenfelder C (1994) Estimation of renal interstitial adenosine and purine metabolites by microdialysis. (springer.com)
- Goldman et al (2013) Purine receptor mediated actin cytoskeleton remodeling of human fibroblasts. (tocris.com)
- CVT-3619 was a partial agonist relative to CPA to reduce lipolysis in epididymal and inguinal adipocytes. (aspetjournals.org)
- Thus, a partial agonist may elicit a maximal response only in tissues in which there is receptor reserve (i.e., tissues wherein submaximal receptor activation nevertheless leads to a maximal functional effect), even when the concentration of agonist is sufficiently high to occupy all receptors. (aspetjournals.org)
- Partial agonist binding appeared both enthalpy and entropy driven. (garvan.org.au)
- Partial agonist binding was significantly dependent on the presence of Thr277 at 25 degrees, whereas such a dependence was not evident at 0 degrees. (garvan.org.au)
- Capadenoson, currently classified as an adenosine A 1 receptor (A 1 AR) partial agonist, has undergone two Phase IIa clinical trials, initially in patients with atrial fibrillation and subsequently in patients with stable angina. (monash.edu)
- Awad AS, Huang L, Ye H et al (2006) Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy. (springer.com)
- These nucleosides exhibit similar selectivities as agonists of the A3 versus the A1 receptor for both human and mouse adenosine receptors, and are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. (nih.gov)
- Selective Activation of Adenosine A2A Receptors on Immune Cells by a CD73-Dependent Prodrug Suppresses Joint Inflammation in Experimental Rheumatoid Arthritis. (painresearchforum.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)
- This is a direct effect on pacemaker cells and is mediated by extracellular adenosine receptors (i.e. (biomedsearch.com)
- During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. (springer.com)
- These results suggests that A1 adenosine receptors mediate a local peripheral antinociceptive effect and the involvement of local peripheral A2 receptors in the enhancement of the algesic response. (nih.gov)
- The potency and receptor subtype selectivity of selected examples was further evaluated by measuring their effects on cAMP accumulation at all human adenosine receptor subtypes expressed in CHO cells. (wiley.com)
- The cubanylmethyl derivative in particular proved to be highly receptor subtype selective. (wiley.com)
- A1 subtype). (biomedsearch.com)
- Another synthetic drug specific to the adenosine A2A receptor subtype is CGS-21680 that has been shown to cause apneas in 14- to 21-day-old rat pups in vivo. (wikipedia.org)
- Adenosine is used as an adjunct to thallous (thallium) chloride TI 201 or Tc99m myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. (wikipedia.org)
- For instance, both A 1 receptors and A 2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A 2A receptor also has broader anti-inflammatory effects throughout the body. (wikipedia.org)
- Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining. (drugbank.ca)
- Objectives In the absence of effective clinical pharmacotherapy for prevention of reperfusion-mediated injury, this study re-evaluated the effects of intracoronary adenosine on infarct size and no-reflow in a porcine model of acute myocardial infarction using clinical bolus and experimental high-dose infusion regimens. (onlinejacc.org)
- Conclusions During reperfusion, intracoronary adenosine can limit infarct size and no-reflow in a porcine model of acute myocardial infarction. (onlinejacc.org)
- More specifically, A1 and A2A receptors play a role in regulating myocardial oxygen consumption and coronary blood flow . (axonmedchem.com)
- Recently, clinical evidence was found for the A3 receptor to be involved in rheumatoid arthritis , among other myocardial functions. (axonmedchem.com)
- One approach to achieve cardioprotection is to enhance myocardial sensitivity to the endogenous adenosine by increasing the number of adenosine receptors instead of administering an adenosine receptor agonist. (garvan.org.au)
- The relative potencies of agonists for the A2B adenosine receptor could only be tested by measurement of receptor-stimulated adenylyl cyclase activity. (biomedsearch.com)
- Blockade of adenosine A2B receptors ameliorates murine colitis. (nih.gov)
- Thus, the administration of an exogenous agonist or increasing the level of an endogenous agonist have similar effects. (rug.nl)
- However, treatment with full A1 AR agonists has been associated with numerous challenges like cardiovascular side effects, off-target activation as well as desensitization of A1 AR leading to tachyphylaxis. (eurekaselect.com)
- In this regard, partial agonists of A1 AR have been found to be beneficial in enhancing insulin sensitivity and subsequently reducing blood glucose level, while avoiding severe CVS side effects and tachyphylaxis. (eurekaselect.com)
- Borea PA, Gessi S, Merighi S, Varani K. Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? (eurekaselect.com)
- the hypothesis is that this bitopic mode would result in unique receptor conformations that will signal to desirable pathways while sparing those pathways mediating undesirable effects. (pnas.org)
- Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. (wikipedia.org)
- The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. (wikipedia.org)
- Adenosine and acetylcholine have similar effects, being additive up to a maximal response, and may be the result of activation of the same K+ channels via different receptors. (biomedsearch.com)
- Agmon Y, Dinour D, Brezis M (1993) Disparate effects of adenosine A1- and A2-receptor agonists on intrarenal blood flow. (springer.com)
- Beach RE, Good DW (1992) Effects of adenosine on ion transport in rat medullary thick ascending limb. (springer.com)
- Beach RE, Watts BA 3rd, Good DW et al (1991) Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions. (springer.com)
- The A2AR is expressed in lung tissues, where it is activated by endogenous/exogenous adenosine or A2AR agonists and where it exerts anti-inflammatory effects ( 24 , 39 , 45 ). (physiology.org)
- Several studies have also suggested that the beneficial effects of adenosine occur through the effects of the A2AR and A2BR ( 7 , 22 , 27 , 43 ). (physiology.org)
- Background Despite the clear cardioprotective effects of adenosine, when administered prior to ischemia, studies on cardioprotection by adenosine when administered at reperfusion have yielded contradictory results in both pre-clinical and clinical settings. (onlinejacc.org)
- These multiple physiologic functions controlled by adenosine receptors result in some undesirable side effects from direct adenosine receptor agonists, including headache, nausea, 5 motor weakness, 6,7 chest pain, and atrioventricular block, 8 which limit their clinical application. (asahq.org)
- All of these findings clearly demonstrate that (1) adenosine mediates the effects of acupuncture, and (2) interfering with adenosine breakdown may prolong the clinical effects of acupuncture. (chiroaccess.com)
- What this elegant series of experiments has shown us is that, at least for one type of acupuncture executed in an animal model, the analgesic effects most commonly attributed to acupuncture have been packaged into a functional receptor for a neurotransmitter. (chiroaccess.com)
- The authors concluded, "These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture. (thecamreport.com)
- Receptors, located on both the cell surface and within the cell, are the molecular targets through which drugs produce their beneficial effects in various disease states. (currentprotocols.com)
- On the other hand adenosine analogues have been shown to possess antinociceptive effects after peripheral and intrathecal administration in animals. (nih.gov)
- Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat. (nih.gov)
- Thus, increasing the receptor level improves the myocyte sensitivity to the endogenous adenosine, which in turn causes all of the cardioprotective effects found for exogenously administered adenosine agonists. (garvan.org.au)
- Flögel and colleagues reported that the anti-inflammatory effects of chet-AMP were due to hydrolysis to chet-adenosine by ecto-5'-nucleotidase (NT5E, also known as CD73) followed by activation of the adenosine A2A receptor. (painresearchforum.org)
- And related, are the anti-inflammatory effects seen in vivo A1 and/or A2A mediated? (painresearchforum.org)
- An Examination of a Nocturnal Frontal Lobe Epilepsy Mutation in Subtypes of Neuronal Nicotinic Acetylcholine Receptors. (alaska.edu)
- Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (Prozac). (currentprotocols.com)
- Barrett RJ, Droppleman DA (1993) Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. (springer.com)
- Cappellacci et al (2005) Synthesis, biological evaluation, and molecular modeling of ribose-modified adenosine analogues as adenosine receptor agonists. (tocris.com)
- NICE 2011) Drugs used to treat hypertension include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium-channel blockers, diuretics and beta-blockers. (acupuncture.org.uk)
- Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes. (semanticscholar.org)
- We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. (deepdyve.com)
- Also, increased expression of the A3 receptor caused an enhanced cardioprotective effect by the preconditioning ischemia. (garvan.org.au)
- The study provides the first proof for the new concept that an increased expression of the human A3 receptor in the cardiac myocyte can be an important cardioprotective therapeutic approach. (garvan.org.au)
- Target selectivity is defined as a difference in target binding to different receptors, and tissue selectivity is defined as a difference in target binding to the same target in different tissues. (springer.com)
- high resolution crystal structure of the M2 muscarinic acetylcholine receptor bound to an activating nanobody (Nb9-8, green), orthosteric agonist (iperoxo, yellow) and positive allosteric modulator (LY2119620, purple). (monash.edu)
- movie showing molecular dynamics simulation of a negative allosteric modulator drug binding to the M2 muscarinic acetylcholine receptor. (monash.edu)
- N6-Cyclopentyladenosine (CPA) is a drug which acts as a selective adenosine A1 receptor agonist. (wikipedia.org)
- Concas et al (1993) Anticonvulsant doses of 2-chloro- N 6 -cyclopentyladenosine, an adenosine A 1 receptor agonist, reduce GABAergic transmission in different areas of the mouse brain. (tocris.com)
- Lohse et al (1988) 2-Chloro- N 6 -cyclopentyladenosine: a highly selective agonist at A 1 adenosine receptors. (tocris.com)
- Increasing extracellular potassium in conjunction with a bath application of the adenosine A1 receptor agonist cyclopentyladenosine induced oscillations similar to ANOs. (inserm.fr)
- N 6 -cyclopentyladenosine) or as mixed A 1 /A 2 receptor agonists (e.g. adenosine, inosine, 5'-(Nethylcarboxamido) adenosine) caused mast cell degranulation, whereas a predominantly A3 receptor agonist (IB-MECA) was inactive. (hindawi.com)
- Human herpes virus KSHV encodes a constitutively active G‐protein‐coupled receptor linked to cell proliferation. (currentprotocols.com)