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 22.214.171.124.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 126.96.36.199.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 188.8.131.52.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.
Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury. (1/77)We recently reported the identification of a novel human adenosine A3 receptor-selective agonist, (2S,3S,4R,5R)-3-amino-5-[6-[5-chloro-2-(3-methylisoxazol-5-ylmethoxy)benzylamino] purin-9-yl]-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide (CP-608,039), with 1,260-fold selectivity for the human A3 versus human A1 receptor (DeNinno et al., J Med Chem 46: 353-355, 2003). However, because the modest (20-fold) rabbit A3 receptor selectivity of CP-608,039 precludes demonstration of A3-mediated cardioprotection in rabbit models, we identified another member of this class, (2S,3S,4R,5R)-3-amino-5-[6-(2,5-dichlorobenzylamino)purin-9-yl]-4-hydroxytetrahyd rofuran-2-carboxylic acid methylamide (CP-532,903), which both retained human A3 receptor selectivity (210-fold; human A3/human A1 Ki: 23/4,800 nM) and had improved rabbit A3 receptor selectivity (90-fold; rabbit A3/rabbit A1 Ki: 23/2,000 nM). Infarct size was measured in Langendorff hearts or in vivo after 30 min of regional ischemia and 120 min of reperfusion. Five-minute perfusion with CP-532,903 before ischemia-reperfusion elicited a concentration-dependent reduction in infarct size in isolated hearts (EC50: 0.97 nM; maximum reduction in infarct size: 77%, P < 0.05 vs. control). Furthermore, administration of CP-532,903 (150 nM) at reperfusion also significantly reduced infarct size by 64% (P < 0.05 vs. control), which was not different (P > or = 0.05) from the cardioprotection provided by the same concentration of drug given before ischemia. The selective rabbit A1 receptor antagonist BWA1433 did not affect CP-532,903-dependent cardioprotection. In vivo, CP-532,903 (1 mg/kg) reduced infarct size by 50% in the absence of significant hemodynamic effects (mean arterial pressure, heart rate, rate-pressure product). CP-532,903 and CP-608,039 represent a novel class of human A3 receptor-selective agonists that may prove suitable for investigation of the clinical cardioprotective efficacy of A3 receptor activation. (+info)
An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation. (2/77)Adenosine, a natural metabolite, plays important roles in several physiological and pathological processes, including modulation of cellular proliferation. Here, we report that among different adenosine analogues tested, micromolar concentrations of the A(3) adenosine receptor (A(3)AR)-selective agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) completely inhibited the growth of the human breast cancer cell lines MCF-7 and ZR-75 while inducing apoptosis in T47D and Hs578T cells, which do not express A(3)AR mRNA. In MCF-7 cells, A(3)AR overexpression did not increase the sensitivity to drug treatment and an A(3)AR antagonist did not abolish IB-MECA effect. In search for mechanisms of the effect of this ligand, we found that in estrogen receptor alpha (ERalpha)-positive cells, IB-MECA rapidly down-regulated ERalpha at mRNA and protein levels and consequently at the transcriptional activity level. Moreover, overexpression of ERalpha in MCF-7 cells alleviated the proliferation inhibition induced by IB-MECA. The inhibitory effects on cell growth and to some extent on ERalpha were mimicked by 2-chloro-adenosine >3'-deoxyadenosine> adenosine but not by a variety of other ligands. Our studies indicate that IB-MECA can down-regulate ERalpha and inhibit proliferation or induce apoptosis in different breast cancer cell types and raise the possibility of using this and related compounds in breast cancer treatment. (+info)
Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced protection from cardiac ischemia. (3/77)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)
Partial agonists for A(3) adenosine receptors. (4/77)Selective agonists for A(3) adenosine receptors (ARs) could potentially be therapeutic agents for a variety of disorders, including brain and heart ischemic conditions, while partial agonists may have advantages over full agonists as a result of an increased selectivity of action. A number of structural determinants for A(3)AR activation have recently been identified, including the N(6)-benzyl group, methanocarba substitution of ribose, 2-chloro and 2-fluoro substituents, various 2'- and 3'-substitutions and 4'-thio substitution of oxygen. The 2-chloro substitution of CPA and R-PIA led to A(3) antagonism (CCPA) and partial agonism (Cl-R-PIA). 2-Chloroadenosine was a full agonist, while 2-fluoroadenosine was a partial agonist. Both 2'- and 3'- substitutions have a pronounced effect on its efficacy, although the effect of 2'-substitution was more dramatic. The 4-thio substitution of oxygen may also diminish efficacy, depending on other substitutions. Both N(6)-methyl and N(6)-benzyl groups may contribute to the A(3) affinity and selectivity; however, an N(6)-benzyl group but not an N(6)-methyl group diminishes A(3)AR efficacy. N(6)-benzyl substituted adenosine derivatives have similar potency for human and rat A(3)ARs while N(6)-methyl substitution was preferable for the human A(3)AR. The combination of 2-chloro and N(6)-benzyl substitutions appeared to reduce efficacy further than either modification alone. The A(2A)AR agonist DPMA was shown to be an antagonist for the human A(3)AR. Thus, the efficacy of adenosine derivatives at the A(3)AR appears to be more sensitive to small structural changes than at other subtypes. Potent and selective partial agonists for the A(3)AR could be identified by screening known adenosine derivatives and by modifying adenosine and the adenosine derivatives. (+info)
Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes. (5/77)Plasma adenosine levels are elevated in cardiovascular disease including hypertension and heart failure, and the nucleoside has been proposed to serve as an endogenous antimyocardial remodeling factor. We studied the modulation of phenylephrine-induced hypertrophy by adenosine receptor activation in isolated neonatal cultured ventricular myocytes. Phenylephrine (10 muM) increased cell size by 35% and significantly increased expression of atrial natriuretic peptide. These effects were reduced by the stable adenosine analog 2-chloroadenosine and were completely blocked by the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (1 microM), the A(2A) receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (100 nM), and the A(3) receptor agonist N(6)-(3-iodobenzyl)adenosine-5'-methyluronamide (100 nM). The antihypertrophic effects of all three agonists were completely reversed by their respective antagonists. Phenylephrine significantly up-regulated expression of the immediate early gene c-fos especially within the first 30 min of phenylephrine treatment. These effects were almost completely inhibited by all adenosine receptor agonists. Although phenylephrine also induced early stimulation of both p38 mitogen-activated protein kinase and extracellular signal-regulated kinase, these responses were unaffected by adenosine agonists. The expression of the G-protein regulatory factors RGS2 and RGS4 were increased by nearly 3-fold by phenylephrine treatment although this was completely prevented by adenosine receptor agonists. These agents also blocked the ability of phenylephrine to up-regulate Na/H exchange isoform 1 (NHE1) expression in hypertrophied myocytes. Thus, our results demonstrate an antihypertrophic effect of adenosine acting via multiple receptor subtypes through a mechanism involving down-regulation of NHE1 expression. The ability to prevent regulators of G-protein signaling (RGS) up-regulation further suggests that adenosine receptor activation minimizes signaling which leads to hypertrophic responses. (+info)
Activation of A3 adenosine receptors attenuates lung injury after in vivo reperfusion. (6/77)BACKGROUND: A3 adenosine receptor (AR) activation worsens or protects against renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the current study were to examine in an in vivo model the effect of A3AR activation on IR lung injury and investigate the mechanism by which it exerts its effect. METHODS: The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A3 receptor agonist IB-MECA (300 microg/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. RESULTS: IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52 +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. CONCLUSIONS: In the feline lung, the A3AR agonist IB-MECA confers a powerful protection against IR lung injury. This effect is mediated by a nitric oxide synthase-independent pathway and involves opening of adenosine triphosphate-sensitive potassium channels. Therefore, selective activation of A3AR may be an effective means of protecting the reperfused lung. (+info)
Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury. (7/77)Activation of either the A(1) or the A(3) adenosine receptor (A(1)R or A(3)R, respectively) elicits delayed cardioprotection against infarction, ischemia, and hypoxia. Mitochondrial contribution to the progression of cardiomyocyte injury is well known; however, the protective effects of adenosine receptor activation in cardiac cells with a respiratory chain deficiency are poorly elucidated. The aim of our study was to further define the role of A(1)R and A(3)R activation on functional tolerance after inhibition of the terminal link of the mitochondrial respiratory chain with sodium azide, in a state of normoxia or hypoxia, compared with the effects of the mitochondrial ATP-sensitive K(+) channel opener diazoxide. Treatment with 10 mM sodium azide for 2 h in normoxia caused a considerable decrease in the total ATP level; however, activation of adenosine receptors significantly attenuated this decrease. Diazoxide (100 muM) was less effective in protection. During treatment of cultured cardiomyocytes with hypoxia in the presence of 1 mM sodium azide, the A(1)R agonist 2-chloro-N(6)-cyclopentyladenosine was ineffective, whereas the A(3)R agonist 2-chloro-N(6)-iodobenzyl-5'-N-methylcarboxamidoadenosine (Cl-IB-MECA) attenuated the decrease in ATP level and prevented cell injury. Cl-IB-MECA delayed the dissipation in the mitochondrial membrane potential during hypoxia in cells impaired in the mitochondrial respiratory chain. In cells with elevated intracellular Ca(2+) concentration after hypoxia and treatment with NaN(3) or after application of high doses of NaN(3), Cl-IB-MECA immediately decreased the elevated intracellular Ca(2+) concentration toward the diastolic control level. The A(1)R agonist was ineffective. This may be especially important for the development of effective pharmacological agents, because mitochondrial dysfunction is a leading factor in the pathophysiological cascade of heart disease. (+info)
CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic effect of 5-fluorouracil in a colon carcinoma murine model. (8/77)NF-kappaB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor (A3AR), inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-kappaB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU) enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma cell proliferation and tumor growth. Downregulation of PKB/Akt, NF-kappaB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU. (+info)
294964902 - EP 1019427 A1 2000-07-19 - N?6 -SUBSTITUTED-ADENOSINE-5 -URONAMIDES AS ADENOSINE RECEPTOR MODULATORS - [origin: WO9906053A1] A series of adenosine-5 -uronamide derivatives bearing N 6 -arylurea, alkarylurea, heteroarylurea, arylcarbonyl, alkarylcarbonyl or heteroarylcarbonyl groups which have affinity and, in some cases, selectivity for the adenosine A1 or A3 receptors are disclosed. These compounds can be used in a pharmaceutical composition to treat disorders caused by excessive activation of the A1 or A3 receptors, or can be used in a diagnostic application to determine the relative binding of other compounds to the A1 or A3 receptors.[origin: WO9906053A1] A series of adenosine-5 -uronamide derivatives bearing N 6 -arylurea, alkarylurea, heteroarylurea, arylcarbonyl, alkarylcarbonyl or heteroarylcarbonyl groups which have affinity and, in some cases, selectivity for the adenosine A1 or A3 receptors are disclosed. These compounds can be used in a pharmaceutical composition to treat
Accumulating evidence supports a therapeutic role of purinergic signaling in cardiac diseases. Previously, efficacy of systemically infused MRS2339, a char
364168652 - EP 2081946 B1 20120530 - ADENOSINE DERIVATIVES FOR THE TREATMENT OF PAIN - [origin: WO2008000745A2] Compounds of formula (I) below are disclosed. Their use as medicaments is described, in particular for the treatment of pain or inflammation. In said Fomula, when X=Y=Z=OH, R SUB 1 /SUB is OCH SUB 2 /SUB CF SUB 2 /SUB CF SUB 3 /SUB , phenoxy (substituted with 3-(4- trifluoromethylphenyl), 3,4-dichloro, (3-trifluoromethyl,4-fluoro), (3-trifluoromethyl,4- chloro), (3-chloro, 4-cyano), or 3,5-bis(trifluoromethyl)), l-piperazinyl(4-(3,4- dichlorophenyl)), phenyl (substituted with 3,4-dichloro, 3,5-difluoro, 3,5- bis(trifluoromethyl) or 3,4,5-trifluoro) or 2-benzofuranyl; or when X=Y=OH and Z=OMe, R SUB 1 /SUB is OCH SUB 3 /SUB , OCH SUB 2 /SUB CHF SUB 2 /SUB , OCH SUB 2 /SUB cyclopentyl, O-(2,5- difluorophenyl) or (S)-sec-butylamino; or when X=H and Y=Z=OH, R SUB 1 /SUB is n-hexylamino or cyclopentylamino; or when (IV) X=Z=OH and Y=H, R SUB 1 /SUB is cyclopentylamino;or a pharmaceutically
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
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f.vtHYTHlNG HER PLAIN AMD CLEAK Consljoljockcn ticcoroer "ALL THATS TttJ« WgLL GIVE TO YO0." No. 2057 PUBLISHED; EVERY TUESDAY AND FRIDAY NOTES OF OUR TOWN i i BMS OF INTEREST GONOBBNINa THE PEOPLE OF OUB BOROOQH CONDENSED FOB RECORDER READERS. William Plank is ill u his boms on Sprint Mill gvenue. Mr. .IM.I Mrs. Harvey field won! to Oettyaburg oa Saturday. •Miss,, Uargare, Wright and i.i n Jones ipral Sunday in WarneravUla. Rev. .111.1 Mrs. .1. F. Shearer an i Itini friends in this borough over Sun-day. \n Intaraatlnc letter from William Henry is published on the third page of this leane. The Penn BoelaJ Club is holdlni - » the P 0. B or .\. Hall every Saturday evening. Rev. Mr. Balnea, of Hanayunk, oon- l"1 : ■ In the BaptIM Church on Sunday morning and evening John Devlin and brothers have loft this place for good to take up their ,,si1 Mount Washington, Pitta-burg, South Bide. The ladles of Calvary Church will i sals 11 Bread and Cakea on Sat-nrday afternoon, November tad ...
Diamond I, Mochly-Rosen D, Gordon AS. In Alcohol and seizures: basic mechanisms and clinical concepts. Porter R, Mattson R, Kramer J and Diamond I (eds). FA Davis, Philadelphia, pp 79-86, (1990). ...
... is a selective adenosine A3 subtype receptor agonist. It has antiinflammatory effects and has been shown to reduce ... The A3 adenosine receptor agonist CP-532,903 [N6-(2,5-dichlorobenzyl)-3'-aminoadenosine-5'-N-methylcarboxamide] protects ... Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic ... Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils. ...
A3 adenosine receptor. Main article: Adenosine A3 receptor. It has been shown in studies to inhibit some specific signal ... Adenosine receptors Receptor. Gene. Mechanism . Effects. Agonists. Antagonists A1 ADORA1. Gi/o → cAMP↑/↓ *Inhibition *↓ ... A1 adenosine receptor. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ...
... 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 ... Müller CE (2003). "Medicinal chemistry of adenosine A3 receptor ligands". Current Topics in Medicinal Chemistry. 3 (4): 445-62 ... with high selectivity over the other three adenosine receptor subtypes (ki values at human A1, A2A and A2B receptors are 4.1, ...
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ... An adenosine A3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis. In a mouse model of ... adenosine receptor". Mol. Pharmacol. 63 (5): 1021-31. doi:10.1124/mol.63.5.1021. PMID 12695530. "Adenosine Receptors: A3". ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... 2002). „A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down- ... Cordeaux Y, Briddon SJ, Alexander SP, Kellam B, Hill SJ (2008). „Agonist-occupied A3 adenosine receptors exist within ... Development of potent and selective human A3 adenosine receptor agonists". Nucleic Acids Symposium Series (2004). 49 (49): 31-2 ...
"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 ...
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 ... A2A receptors are not found in neurons that express the dopamine receptor D1 receptors and Substance P. Within the striatum, ... and signal transduction in the form of cyclic adenosine monophosphate (cAMP). A2B and A3 receptors require concentrations of ...
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor. ... Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Extracellular ... Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor. However, while it is able to increase ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry. 46 (7 ... 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 ... The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it. This ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry 46 (7 ... Sullivan GW (November 2003). "Adenosine A2A receptor agonists as anti-inflammatory agents". Current Opinion in Investigational ... 1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): ...
"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. ...
Adenosine diphosphate (ADP) is a platelet agonist. When it is added to saline-diluted whole blood in the test cuvette, it ... Thrombin receptor activating peptide-6 (TRAP-6) activates platelets through the thrombin receptor protease activated receptor-1 ... Prostaglandin E1 (PGE1) is a platelet inhibitor that causes an increase in cyclic adenosine monophosphate (cAMP) in platelets ... Activation of the P2Y1 receptor initiates platelet aggregation in response to ADP. The P2Y1 receptor is required for ADP- ...
On the other hand, nanomolar concentrations of adenosine activate A1 and A3 receptors, resulting in neutrophilic chemotaxis ... 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 ...
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...
Valerian also contains isovaltrate, which has been shown to be an inverse agonist for adenosine A1 receptor sites. This action ... doi:10.1213/01.ANE.0000096189.70405.A5. PMID 14742369. Wills, R.B.H. & Shohet, D. (July 2009). "Changes in valerenic acids ... 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. ...
D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... 18 E3,18 55.78 cM. Start. 82,392,496 bp. End. 82,406,777 bp. ... Galanin receptor 1 (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene. ... "Galanin Receptors: GAL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
Agonists. *Neurokinin B - endogenous peptide ligand, also interacts with other neurokinin receptors but has highest ... "Tachykinin Receptors: NK3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... tachykinin receptor activity. • G-protein coupled receptor activity. • signal transducer activity. • protein binding. ... "Entrez Gene: TACR3 tachykinin receptor 3".. *^ Quartara L, Altamura M (Aug 2006). "Tachykinin receptors antagonists: from ...
"C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained agonist-induced signaling. Role of receptor ... tachykinin receptor activity. • G-protein coupled receptor activity. • substance K receptor activity. • signal transducer ... "Tachykinin Receptors: NK2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Agonists. *GR-64349 - potent and selective agonist, EC50 3.7nM, 7-amino acid polypeptide chain. CAS# 137593-52-3 ...
This is called constitutive activity, and it means that the receptor is always "on," unless acted on by an inverse agonist. ... dopamine receptor type 2 (DRD2), melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT2c receptor). See ... Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth ... 3,3 A3. Start. 27,371,351 bp. End. 27,378,010 bp. RNA expression pattern. ...
B receptor agonists along with a selective GABAB antagonist or selective agonists for the GHB receptor which are not agonists ... Receptor/signaling modulators. GABA receptor modulators. Glutamate receptor modulators. Glycine receptor modulators. ... The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is a G protein-coupled receptor (GPCR) that ... The function of the GHB receptor appears to be quite different from that of the GABAB receptor. It shares no sequence homology ...
D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, ... 7 E3,7 55.86 cM. Start. 105,425,731 bp. End. 105,470,898 bp. ... type B gastrin/cholecystokinin receptor binding. • gastrin receptor activity. • cholecystokinin receptor activity. • peptide ... "Entrez Gene: CCKBR cholecystokinin B receptor".. *^ Altar CA, Boyar WC (Apr 1989). "Brain CCK-B receptors mediate the ...
Activation of δ receptors produces analgesia, perhaps as significant potentiators of mu-opioid agonists.[clarification needed] ... The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an inhibitory 7- ... δ−opioid receptors have been shown to interact with β2 adrenergic receptors, arrestin β1 and GPRASP1. ... opioid receptor activity. • protein binding. • receptor serine/threonine kinase binding. Cellular component. • cytoplasm. • ...
... such as the μ agonist etorphine and the κ agonist bremazocine, have been shown to act as agonists for this effect (even in the ... When the adenylyl cyclase enzyme complex is stimulated, it results in the formation of Cyclic Adenosine 3', 5'-Monophosphate ( ... ε opioid receptor. Another postulated opioid receptor is the ε opioid receptor. The existence of this receptor was ... Additional receptors. Sigma (σ) receptors were once considered to be opioid receptors due to the antitussive actions of ...
... a selective 5-HT1B receptor inverse agonist". CNS Drug Reviews. 7 (4): 433-44. doi:10.1111/j.1527-3458.2001.tb00209.x. PMC ... 9 E1,9 44.61 cM. Start. 81,628,291 bp. End. 81,633,828 bp. ... RU-24969 (mixed 5-HT1A/1B agonist). Partial agonists. * ... 5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene.[ ... G-protein coupled receptor activity. • signal transducer activity. • G-protein coupled serotonin receptor activity. • protein ...
157 (1): 148.e1-148.e5. doi:10.1016/j.ahj.2008.09.017. Drepper, Michael D; Spahr, Laurent; Frossard, Jean Louis (2012-05-14). " ... is suggested to bind covalently to CYS17 or CYS270 of the P2Y12 receptor and therefore blocking the binding of the agonist. ... P2Y12 receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y12 receptor that leads to ... Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute ...
Leukotriene-A4 hydrolase), or are the cellular receptors responsible for mediating the cellular responses to the down-stream ... As a second drug added to corticosteroids, leukotriene inhibitors appear inferior to Beta2-adrenergic agonist drugs in the ... An Adenosine triphosphate (ATP) binding site; ATP is crucial for ALOX5's metabolic activity ... Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ...
... is an A3AR selective agonist containing multiple receptor affinity- and selectivity-enhancing modifications and a therape ... is an A3AR selective agonist containing multiple receptor affinity- and selectivity-enhancing modifications and a therapeutic ... These data will be useful to guide rational design of drugs targeting A3AR, considering efficacy, metabolic elimination, and ... Metabolic mapping of A3 adenosine receptor agonist MRS5980 Zhong-Ze Fang;Dilip Tosh;Naoki Tanaka;Haina Wang;Kristopher Krausz; ...
A2B and A3, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A3AR (hA3AR) subtype is implicated in ... elucidate the binding of agonists to the A3AR and discuss the challenges associated with an accurate prediction of the receptor ... Therefore, hA3AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, ... Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, ...
7. U.S. Provisional Application 62/033,723, filed August 6, 2014, titled "A3 Adenosine Receptor Agonists" [HHS Ref. No. E-210- ... 1. U.S. Patent 8,735,407, issued May 27, 2014, titled "Purine Derivatives As A3 Adenosine Receptor-Selective Agonists" [HHS Ref ... 6. U.S. Provisional Application 61/909,742, filed November 27, 2013, titled "A3 Adenosine Receptor Agonists" [HHS Ref. No. E- ... The subject inventions describe selective A3 Adenosine Receptor (A3AR) agonists, and their in vivo activity reducing or ...
N)-Methanocarba Adenosine Derivatives and Their Dendrimer Conjugates as A3 Receptor Agonists (U.S. Patent Application Number 61 ... N)-Methanocarba Adenosine Derivatives and Their Dendrimer Conjugates as A3 Receptor Agonists (U.S. Patent Application Number 61 ... Disclosed are (N)-methanocarba adenine nucleosides, e.g., of the formula (I): as A3 adenosine receptor agonists, pharmaceutical ... which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) ...
Adenosine A3 receptor agonist inhibits retinal ganglion cell apoptosis in vivo Joana Galvao; Li Guo; Ana Raquel Santiago; ... Adenosine A3 receptor agonist inhibits retinal ganglion cell apoptosis in vivo You will receive an email whenever this article ... Joana Galvao, Li Guo, Ana Raquel Santiago, Antonio Ambrosio, M Francesca Cordeiro; Adenosine A3 receptor agonist inhibits ... Adenosine and three of its four receptors have been identified at the level of retinal ganglion cell (RGC) layer. Our previous ...
The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB ... The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB ... The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB ... The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB ...
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 ...
Structural Characterization of Agonist Binding to A3 Adenosine Receptor through Biomolecular Simulations and Mutagenesis ... A3 adenosine receptor agonist cAMP IB-MECA GPCR molecular dynamics mutant receptor MM-GBSA Molecular Mechanics The Generalized ... Structural Characterization of Agonist Binding to A3 Adenosine Receptor through Biomolecular Simulations and Mutagenesis ...
Choi, IY, Lee, JC, Ju, C, Hwang, S, Cho, GS, Lee, HW, Choi, WJ, Jeong, LS & Kim, W-K 2011, A3 adenosine receptor agonist ... A3 adenosine receptor agonist reduces brain ischemic injury and inhibits inflammatory cell migration in rats. / Choi, In Young ... A3 adenosine receptor agonist reduces brain ischemic injury and inhibits inflammatory cell migration in rats. American Journal ... A3 adenosine receptor agonist reduces brain ischemic injury and inhibits inflammatory cell migration in rats. In: American ...
Can-Fite moves towards opening Phase 3 study of adenosine A3 receptor agonist, CF101 in rheumatoid arthritis ... A3 receptor expression will be determined prior to dosing and correlated with efficacy. Of interest, Can-Fite is developing a ... A3 receptors are over-expressed in rheumatoid arthritis and this correlates with lower disease activity suggesting a possible ... Can-Fite is developing A3 agonist, CF101 for rheumatoid arthritis and psoriasis. ...
Thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, suppresses angiogenesis by regulating PI3K/AKT/mTOR and ERK signaling ... Thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, suppresses angiogenesis by regulating PI3K/AKT/mTOR and ERK signaling ... In the present study, we assayed the anti-angiogenic activity of thio-Cl-IB-MECA, a novel A3AR agonist, in cultured HUVECs and ... Although A3AR agonists exhibit a variety of biological activities including anticancer effects, their possible anti-angiogenic ...
Adenosine. approved, investigational. yes. agonist. Details. DB05511. Piclidenoson. investigational. unknown. Details. DB00824 ... Adenosine receptor A3. Details. Name. Adenosine receptor A3. Synonyms. Not Available. Gene Name. ADORA3. Organism. Humans. ... G-protein coupled adenosine receptor activity. Specific Function. Receptor for adenosine. The activity of this receptor is ... Sajjadi FG, Firestein GS: cDNA cloning and sequence analysis of the human A3 adenosine receptor. Biochim Biophys Acta. 1993 Oct ...
A3 adenosine receptor agonist. Rheumatoid arthritis. Completed enrollment of about 50% of the 525 patients planned for the ... Dual 5-HT 1b/1d receptor agonist; cyclooxygenase 2 inhibitor. Migraine. Enrollment of about 300 participants completed in ... 5-HT 2a receptor antagonist; opioid receptor sigma antagonist 2. Schizophrenia. Enrollment completed in pivotal trial assessing ... Neurokinin-1 receptor antagonist. Pruritus in atopic dermatitis. Epione trial in adults did not meet its primary endpoint in ...
A3 adenosine receptor. Main article: Adenosine A3 receptor. It has been shown in studies to inhibit some specific signal ... Adenosine receptors Receptor. Gene. Mechanism . Effects. Agonists. Antagonists A1 ADORA1. Gi/o → cAMP↑/↓ *Inhibition *↓ ... A1 adenosine receptor. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b And A3 Adenosine Receptors. ...
A3 adenosine receptor agonists. Disclosed are compounds of the formula (I) and (II) which are A.sub.3 adenosine receptor ... Substituted 4-azaindoles and their use as GluN2B receptor modulators. Substituted 4-azaindoles as NR2B receptor ligands. Such ... Substituted pyrazino[1,2-a]indoles as sigma receptor activity modulators. The invention refers to compounds of general formula ... Substituted 5-membered heterocyclic analogs as protease activated receptor 4 (PAR-4) antagonists. Embodiments of the invention ...
A3 ADENOSINE RECEPTOR AGONISTS. Disclosed are compounds of the formula (I) and (II): ##STR00001## which are A.sub.3 adenosine ... Problem] To provide a compound which can be used as an MC.sub.4 receptor agonist. [Means for Solution] The present inventors ... receptor agonists, pharmaceutical compositions comprising such... 2018/0230149. INHIBITING THE TRANSIENT RECEPTOR POTENTIAL A1 ... DIAMINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE A4 HYDROLASE. This invention is directed to compounds of formula (I): ## ...
Synthesis and evaluation of new N6-substituted adenosine-5-N-methylcarboxamides as A3 adenosine receptor agonists. ... Dual acting antioxidant A1 adenosine receptor agonists.. Gregg A, Bottle SE, Devine SM, Figler H, Linden J, White P, Pouton CW ... 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 adenosine receptor agonist allosteric enhancers having improved potency. ... 2-Amino-3-aroyl-4,5-alkylthiophenes: agonist allosteric enhancers at human A(1) adenosine receptors. ...
Adenosine A3 receptor agonist. Adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. 2 mg ... Piclidenoson (CF-101, Can-Fite Biopharma) is an orally bioavailable, selective A3 adenosine receptor agonist.34 It down- ... Anti-IL-17 receptor mAb. Adults with moderate-to-severe plaque psoriasis. 140 mg or 210 mg SC every 2 or 4 weeks, depending on ... Brodalumab (AstraZeneca/Valeant), an mAb that acts as an IL-17 receptor antagonist, was developed specifically to treat adults ...
CP-532,903 is a selective adenosine A3 subtype receptor agonist. It has antiinflammatory effects and has been shown to reduce ... The A3 adenosine receptor agonist CP-532,903 [N6-(2,5-dichlorobenzyl)-3-aminoadenosine-5-N-methylcarboxamide] protects ... Novel N6-substituted adenosine 5-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic ... Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils. ...
Calbiochem CAS 163042-96-4 A highly selective agonist of adenosine A3 receptor (Ki = 330 pM) - Find MSDS or SDS, a COA, data ... Adenosine A₃ Receptor Agonist, 2-Cl-IB-MECA - CAS 163042-96-4 - ... A highly selective agonist of adenosine A3 receptor (Ki = 330 pM). More,, A highly selective agonist of adenosine A3 receptor ( ... An adenosine analog that acts as a highly selective agonist of adenosine A3 receptor (Ki = 330 pM, 820 nM, 470 nM for A3, A1 ...
10.8.1 CF101 (adenosine A3 receptor agonist) - Can-Fite BioPharma and OphthaliX. 10.8.2 FST-100 (povidone-iodine/dexamethasone ... 10.4.6 Tandospirone (serotonin 1A agonist) - Alcon (Novartis). 10.4.7 UF-021 (unoprostone) - R-TechUeno. 10.5 Drugs in Phase 2 ... 10.14.2 Kineret (anakinra: IL-1 receptor antagonist) - Amgen/Sobi. 10.15 Other Drugs in the Development Pipeline for Ophthalmic ... 10.13.3 Tavilermide (formerly MIM-D3tyrosine kinase receptor antagonist) - Allergan. 10.13.4 SI-614 (modified hyaluronate) - ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... 2002). „A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down- ... Cordeaux Y, Briddon SJ, Alexander SP, Kellam B, Hill SJ (2008). „Agonist-occupied A3 adenosine receptors exist within ... Development of potent and selective human A3 adenosine receptor agonists". Nucleic Acids Symposium Series (2004). 49 (49): 31-2 ...
... receptor agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected to 30 min of regional ischemia and ... Furthermore, combining zopolrestat with an A(3) agonist allows a reduction in the zopolrestat concentration while maintaining ... either alone or in combination with an adenosine A(3)- ... Relative importance of adenosine A1 and A3 receptors in ... Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.. *W R Tracey, W Magee, +4 ...
A3 adenosine receptor agonists US5589467A (en) 1993-09-17. 1996-12-31. Novo Nordisk A/S. 2,5,N6-trisubstituted adenosine ... Activation of natural killer cells by adenosine A3 receptor agonists US20030013675A1 (en) 2001-05-25. 2003-01-16. Boehringer ... Use of an adenosine a3 receptor agonist for inhibition of viral replication ... N-pyrazole A2A adenosine receptor agonists US6214807B1 (en) 1999-06-22. 2001-04-10. Cv Therapeutics, Inc.. C-pyrazole 2A A ...
AntagonistsA3ARLigandsSubtypesEndogenousEffects of adenosineSubtypeInhibitionAbstractPharmacologyDerivativesApoptosisTherapeuticAffinityExtracellular adenosineInverse agonistsAnti-inflammatoryEffect of adenosine receptor activationActivatesADORA3NECASuggest that adenosineSuppressesNucleosidePurineHumanActivation of adenosineMurinePurinergicOrally bioavailableDeaminaseNitric OxideRatsSelectivitySmall moleculePharmacologicalModulatesLigandProteinsProteinMoleculeGeneNeutrophilsStimulationPiclidenosonShow that adenosineInflammationCCPAAdenylyl cyclaseCharacterizationMyocardial
- Such conjugates are have the potential of being used as dual agonists, dual antagonists, or agonist/antagonist combinations. (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)
- 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)
- Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). (wikipedia.org)
- 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)
- 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)
- 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)
- 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)
- Adenosine receptors: development of selective agonists and antagonists. (wikipathways.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)
- Finally, in lymphocytes, activation of A3 receptor subtype would result in a reduction of the accession of killer T cells to tumor cells by exerting an immunosuppressive effect and suggesting a role for antagonists of this receptor as anti-tumoral drugs. (unife.it)
- Synthetic selective ligands that either mimic the action of adenosine (i.e. agonists) in a fashion specific at a single subtype, or suppress it (i.e. antagonists), can be applied with great benefit in models of disease states, and therefore such agents are being explored as potential pharmaceuticals. (grantome.com)
- Our novel selective A3AR agonists and antagonists containing a methanocarba (bicyclo3.1.0hexane) ribose-ring substitution constrained in the receptor-preferred North (N) conformation have improved pharmacological profiles. (grantome.com)
- Indeed, when adenosine is eliminated from PMN suspensions by the addition of adenosine deaminase, or when cells are incubated with adenosine A 2a receptor antagonists, important quantities (40-80 pmol/10 6 cells) of 5-lipoxygenase products are synthesized by PMN incubated with 1 to 5 μM exogenous AA. (aspetjournals.org)
- This AA-induced Ca 2+ mobilization, as well as the corresponding 5-lipoxygenase translocation and stimulation of LT synthesis, was blocked efficiently by the LT synthesis inhibitor MK0591, the LTB 4 receptor antagonists CP105696 and LY223982, and the LTA 4 hydrolase inhibitor SC57461A. (aspetjournals.org)
- TLR agonists have demonstrated great potential as antimicrobial agents and vaccine adjuvants, whereas TLR antagonists are being developed as reagents and drugs to dampen immune responses. (bvsalud.org)
- Our previous studies have shown that RGCs express the A3AR, and that the A3AR agonist is protective against an NMDA insult to retinal explants. (arvojournals.org)
- In this study, we focused on assessing A3AR expression and the potential neuroprotective effects of a selective A3AR agonist, 2-Cl-IB-MECA, in two rat models of RGC degeneration: partial optic nerve transection (pONT) and ocular hypertension model (OHT). (arvojournals.org)
- Treatment with the A3AR agonist resulted in a reduction of IOP in OHT eyes. (arvojournals.org)
- Rats treated with both A3AR agonist and antagonist did not show significant difference from insult alone. (arvojournals.org)
- The A3 adenosine receptor (A3AR) is highly expressed in tumors and was suggested as a target for cancer treatment. (spandidos-publications.com)
- The high expression level of the receptor was directly correlated to overexpression of NF-κB, known as a transcription factor of A3AR. (spandidos-publications.com)
- CF102, a synthetic highly selective agonist to A3AR induced a marked dose response inhibition of tumor growth in N1S1 HCC tumor rats, via de-regulation of the NF-κB and the Wnt signal transduction pathways, resulting in apoptosis of tumor cells. (spandidos-publications.com)
- however, the mechanism underlying anti-ischemic protection by the A3AR agonist remains unclear. (elsevier.com)
- Here, we report that 2-chloro-N 6 -(3-iodobenzyl)-5′-N-methylcarbamoyl-4′-thioadenosine (LJ529), a selective A3AR agonist, reduces inflammatory responses that may contribute to ischemic cerebral injury. (elsevier.com)
- BioIntervene's BIO-205 is an A3 adenosine receptor (A3AR) agonist, which means it homes in on and activates the A3 receptor on adenosine. (xconomy.com)
- The article is titled "Engagement of the GABA to KCC2 Signaling Pathway Contributes to the Analgesic Effects of A3AR Agonists in Neuropathic Pain. (bioquicknews.com)
- For this reason, Dr. Salvemini and colleagues teamed up with researchers from the NIH, the University of Arizona, and two institutes in Quebec, Canada, to investigate a new target for treating chronic pain: the A3 adenosine receptor (A3AR). (bioquicknews.com)
- Adenosine acts as a regulatory signaling molecule in other areas of the nervous system, so we hypothesized that A3AR might also play a role in regulating pain signals during pain processing. (bioquicknews.com)
- Our ongoing program to develop selective A3AR agonists has resulted in advanced clinical trials of two nucleosides. (grantome.com)
- Currently, A3AR agonists discovered in our lab (IB-MECA and Cl-IB-MECA) are developed for the treatment of inflammatory diseases including rheumatoid arthritis and psoriasis;dry eye syndrome;and liver diseases such as hepatocellular carcinoma. (grantome.com)
- Sterically constrained ((N )-methanocarba) adenosine derivatives were nanomolar full agonists of the A3AR and highly selective. (grantome.com)
- She added that A3AR agonists are already in advanced clinical trials as anti-inflammatory and anticancer agents and show good safety profiles. (psychcentral.com)
- These studies suggest that A3AR activation by highly selective small molecular weight A3AR agonists such as MRS5698 activates a pain-reducing pathway supporting the idea that we could develop A3AR agonists as possible new therapeutics to treat chronic pain," Salvemini said. (psychcentral.com)
- IB-MECA, an A3AR agonist, inhibits the growth of different cancer cell types like melanoma, colon, breast, leukemia, and prostate IB-MECA was able to inhibit forskolin-stimulated cAMP levels with an EC50 value of 0.82 μM in OVCAR-3 cells. (bioll.com)
- The company technology platform is based on the finding that the Gi protein coupled A3 adenosine receptor (A3AR) is highly expressed in inflammatory and cancer cells whereas low expression is found in normal body cells. (canfite.com)
- The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. (ekja.org)
- Blocking ADK activity in the spinal cord provided greater than 90% attenuation of OIH and antinociceptive tolerance through A3 adenosine receptor (A3AR) signaling. (bvsalud.org)
- Supplementing adenosine signaling with selective A3AR agonists blocked OIH and antinociceptive tolerance in rodents of both sexes. (bvsalud.org)
- These findings suggest A3AR-dependent adenosine signaling is compromised during sustained morphine to allow the development of morphine-induced adverse effects. (bvsalud.org)
- These findings raise the intriguing possibility that A3AR agonists may be useful adjunct to opioids to manage their unwanted effects. (bvsalud.org)
- We report that in rodents, these adverse effects are due to reduced adenosine signaling at the A3AR, resulting in NOD-like receptor pyrin domain-containing 3-interleukin-1ß neuroinflammation in spinal cord. (bvsalud.org)
- These effects are attenuated by A3AR agonists, suggesting that A3AR may be a target for therapeutic intervention with selective A3AR agonist as opioid adjuncts. (bvsalud.org)
- Also disclosed are conjugates comprising a dendrimer and one or more ligands, which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. (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)
- Multivalent site-specific phage modification enhances the binding affinity of receptor ligands. (nih.gov)
- A number of selective A3 ligands are available. (wikipedia.org)
- Recent developments in adenosine receptor ligands and their potential as novel drugs. (springer.com)
- 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 cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands. (biomedsearch.com)
- The more that is known about the 3-dimensional structure of the target receptor, the easier it is to design appropriate ligands. (grantome.com)
- The rational design of AR ligands was greatly advanced by the recent elucidation of both the agonist-bound (activated) and antagonist-bound (inactive) states of the A2AAR. (grantome.com)
- We are now using this structure advantageously for in silico screening to discover new chemically diverse ligands and to modify existing ligands in ways made possible only through a detailed understanding of molecular recognition and activation of the receptor. (grantome.com)
- Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A 1 , A 2A , A 2B and A 3 , which belong to the G protein-coupled receptor (GPCR) superfamily. (mdpi.com)
- Although there are four adenosine receptor (AR) subtypes, the A2AAR is both highly expressed on lymphocytes and known as a prime mediator of adenosine's anti-inflammatory effects. (jimmunol.org)
- Cells that express one or more of the four G protein-coupled adenosine receptors (AR) subtypes (A1, A2A, A2B, and/or A3) have the capacity to respond to extracellular adenosine. (jimmunol.org)
- Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
- Four adenosine receptor subtypes of the family of G protein-coupled receptors, designated A1, A2A, A2B and A3 are currently known. (biomedsearch.com)
- 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)
- In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. (biomedsearch.com)
- Adenosine is an endogenous and ubiquitous nucleoside that exerts many biological functions through interaction with 4 distinct subtypes of G protein-coupled receptors divided into A1, A2A, A2B, and A3. (unife.it)
- Although adenosine activates multiple receptor subtypes (A1, A2a, A2b, and A3 receptors), the adenylyl cyclase stimulatory A2a adenosine receptors (A2aARs) are regarded mainly as cardioprotective receptors ( 1 ). (pnas.org)
- The adenosine receptors (or P1 receptors ) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand . (wikipedia.org)
- Yang T, Shen JB, Yang R, Redden J, Dodge-Kafka K, Grady J, Jacobson KA, Liang BT (2014) Novel cardioprotective role of endogenous cardiac myocyte P2X4 receptors in heart failure. (springer.com)
- Adenosine is an endogenous purine nucleoside that modulates a wide range of physiological functions ( 1 ). (jimmunol.org)
- Adenosine is an important mediator of the endogenous defense against ischemia-induced injury in the heart. (garvan.org.au)
- 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)
- 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)
- 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 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)
- In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. (biomedsearch.com)
- We report here that the apparent inability of isolated human polymorphonuclear leukocytes (PMNs) to efficiently transform arachidonic acid (AA) is the consequence of A 2a receptor engagement by endogenous adenosine accumulating in incubation media. (aspetjournals.org)
- Barrett RJ, Droppleman DA (1993) Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. (springer.com)
- 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)
- 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)
- The haemodynamic effects of adenosine are thought to result in part from a release of mast cell amines via A3 receptor stimulation. (hindawi.com)
- 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)
- 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)
- The new study, led by Daniela Salvemini, Ph.D., a professor of pharmacological and physiological sciences at Saint Louis University, demonstrated that activation of the A3 adenosine receptor subtype is key in mediating the pain relieving effects of adenosine. (psychcentral.com)
- It has long been appreciated that harnessing the potent pain-killing effects of adenosine could provide a breakthrough step towards an effective treatment for chronic pain," Salvemini said. (psychcentral.com)
- The cardiovascular protective effects of adenosine have been described in recent years. (pnas.org)
- CP-532,903 is a selective adenosine A3 subtype receptor agonist. (wikipedia.org)
- By agonizing with these molecules this particular receptor subtype, we've been able to get away from side effects that are seen when you agonize other adenosine receptors, and really have a pure analgesic effect," he said. (xconomy.com)
- The A1 subtype showed the typical pharmacological profile with 2-chloro-N6-cyclopentyladenosine (CCPA) as the agonist with the highest affinity and a marked stereoselectivity for the N6-phenylisopropyladenosine (PIA) diastereomers. (biomedsearch.com)
- In the past most of the anti-inflammatory effects of this nucleoside were thought to be due to the activation of the A2A subtype, however more recently, the involvement of the A3 subtype has been also considered relevant for the outcome of inflammation. (unife.it)
- This will allow future research to design more effective agonists of the ARs in principle with fewer side effects due to high specificity for a particular receptor subtype. (grantome.com)
- 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)
- 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)
- Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A₃ receptor agonist on hematopoiesis in sublethally γ-irradiated mice. (semanticscholar.org)
- In April 2018, Can-Fite published a paper titled "Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A3 Adenosine Receptor Agonist Piclidenoson" ( https://www.hindawi.com/journals/jir/aip/2310970/ ) in the Journal of Immunology Research. (businesswire.com)
- Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells. (banglajol.info)
- Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. (wikipathways.org)
- Inhibition of experimental auto-immune uveitis by the A3 adenosine receptor agonist CF101. (bio-protocol.org)
- In particular, the activation of the A3 receptor on this cellular type leads to the inhibition of degranulation and superoxide anion production with consequent anti-inflammatory effects. (unife.it)
- Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
- Graphical abstract (1 S ,2 R ,3 S ,4 R ,5 S )-4-(2-((5-Chlorothiophen-2-yl)ethynyl)-6-(methylamino)-9 H -purin-9-yl)-2,3-dihydroxy- N -methylbicyclo[3.1.exane-1-carboxamide ( MRS5980) is an A 3 AR selective agonist containing multiple receptor affinity- and selectivity-enhancing modifications and a therapeutic candidate drug for many inflammatory diseases. (ovid.com)
- abstract = "Adenosine released into the extracellular space by immunologic and nonimmunologic stimuli has been shown to regulate various immune functions. (utmb.edu)
- In this study, we focused on assessing the A3 receptor and its modulation using the A3 agonist, 2-Cl-IB-MECA, in a rat model of RGC apoptosis. (arvojournals.org)
- The potential neuroprotective effect of the A3 adenosine receptor agonist 2-Cl-IB-MECA was assessed using three different concentrations (1.2 µM, 6 µM and 12 µM) in a model of chemical induced RGC apoptosis (intravitreal injection of 8% DMSO was used in Dark Agouti rats). (arvojournals.org)
- Moreover, the agonist 2-Cl-IB-MECA has neuroprotective effects on RGC apoptosis in vivo. (arvojournals.org)
- Targeted overexpression of lymphocyte CD73 revealed that increased adenosine resultant from enhanced CD73 expression contributes to thymocyte apoptosis in adenosine deaminase deficiency ( 9 ). (jimmunol.org)
- IC50 value: 0.11 μM (EC50) Target: adenosine A3 receptor in vitro: IB-MECA has been shown to play important roles in cell proliferation and apoptosis in a variety of cancer cell lines. (bioll.com)
- Additional studies suggest that adenosine induces apoptosis of human arterial smooth muscle cells, which is mediated via the A2bAR in a cAMP-dependent pathway ( 7 ). (pnas.org)
- Adenosine receptors (AR) have been considered as potential therapeutic targets in neurodegenerative diseases, such as glaucoma. (arvojournals.org)
- Because adenosine has such potent effects on inflammation, modulators of adenosine signaling are being evaluated as potential therapeutic options for diseases that have an inflammatory component ( 8 ). (jimmunol.org)
- 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)
- A(1) adenosine receptor agonists: medicinal chemistry and therapeutic potential. (wikipathways.org)
- The receptor is overexpressed in inflammatory and cancer cells, while low expression is found in normal cells, rendering the A 3 AR as a potential therapeutic target. (uconn.edu)
- High affinity and extremely selective A 3 adenosine receptor agonist (K i = 0.33 nM). (tocris.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)
- The antagonist affinity for a given receptor is traditionally considered to be constant, reflecting the chemical nature of the specific ligand-receptor interaction. (aspetjournals.org)
- Therefore, we studied the influence of different agonists on antagonist affinity measurements for G i - and G s -coupled conformations of the adenosine A1-receptor in Chinese hamster ovary cells stably expressing the human adenosine A1-receptor and a cAMP-response element (CRE)-secreted placental alkaline phosphatase reporter gene. (aspetjournals.org)
- However, the antagonist affinity values measured at the G i -coupled and G s -coupled conformations of the receptor were the same in both functional responses and whole-cell binding. (aspetjournals.org)
- Consequently, antagonist affinity measurements at a given species homolog of a particular receptor should remain constant regardless of the method used to measure it, provided that the chemical composition of the receptor has not changed. (aspetjournals.org)
- Antagonist affinity estimates at many GPCRs may indeed depend upon the nature of the agonist used. (aspetjournals.org)
- 2-Chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA)--a high affinity agonist radioligand for A1 adenosine receptors. (wikipathways.org)
- IC50 value: 1nM, 1.1μM and 2 μM (EC50, for PPARδ, -α, and -γ) Target: PPAR in vivo: GW0742 is a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. (bioll.com)
- IC50 value: 7 nM (Ki, fot androgen receptor) Target: androgen receptor in vitro: RAD140 demonstrates excellent affinity for the androgen receptor (Ki = 7 nM) as well as good selectivity over other steroid hormone nuclear receptors, with the closest off target receptor being the progesterone receptor (IC50 = 750 nM). (bioll.com)
- Synergistic effect of granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on neutrophil production in mice. (semanticscholar.org)
- Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. (jimmunol.org)
- The half-life of extracellular adenosine is on the order of seconds, as it is removed from the extracellular space either by adenosine deaminase, which converts it to inosine, or by cellular reuptake via equilibrative or concentrative nucleoside transporters ( 6 , 7 ). (jimmunol.org)
- Therefore, acute increases in extracellular adenosine levels tend to only have local and tissue-limited effects. (jimmunol.org)
- During inflammation, increases in extracellular adenosine levels effectively turn off the local inflammatory response to protect against excessive cellular damage to the surrounding tissue ( 2 ). (jimmunol.org)
- We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. (physiology.org)
- The mechanism of AA-induced stimulation of LT synthesis observed in the absence of extracellular adenosine was investigated. (aspetjournals.org)
- ZM241385, DPCPX, MRS1706 are inverse agonists with different relative intrinsic efficacies on constitutively active mutants of the human adenosine A2B receptor. (wikipathways.org)
- Muller C.E. 2-Phenylimidazo[2,1-i]purin-5-ones: Structure-activity relationships and characterization of potent and selective inverse agonists at human A3 adenosine receptors. (osi.lv)
- Therefore, hA 3 AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. (mdpi.com)
- 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)
- The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease. (springer.com)
- The G i -coupled A 3 adenosine receptor (A 3 AR) mediates anti-inflammatory, anticancer and anti-ischemic protective effects. (uconn.edu)
- The present review summarizes preclinical and clinical human studies demonstrating that A 3 AR agonists induce specific anti-inflammatory and anticancer effects via a molecular mechanism that entails modulation of the Wnt and the NF-κB signal transduction pathways. (uconn.edu)
- It is known that the interaction with the adenosine A3 receptor inhibits several activities of these cells including the release of TNF-alpha and other potent inflammatory cytokines such as IL-6 and IL-8 and increases the production of IL-10 with anti-inflammatory activity. (unife.it)
- Moreover, adenosine protects against renal ischemic reperfusion injury by the anti-inflammatory effect of enhancing the activity of regulatory T cell and by attenuating the inflammatory injury produced by neutrophils via A 2 AR activation. (springer.com)
- Upon subcutaneous administration, abaloparatide acts similar to PTHrP and targets, binds to and activates parathyroid hormone 1 (PTH1) receptor (PTH1R), a G protein-coupled receptor (GPCR) expressed in osteoblasts and bone stromal cells. (cancer.gov)
- Subsequent triggering of chemokine receptors through chemokines then activates leukocyte integrins and allows firm adhesion of the cell. (ahajournals.org)
- Adenosine liberated by this process activates surface adenosine A 2B receptors, results in endothelial junctional reorganization, and promotes barrier function. (jimmunol.org)
- 5′-AMP is rapidly converted to adenosine (via surface-expressed CD73), and adenosine liberated in this fashion directly activates surface adenosine A 2B receptors ( 4 , 7 , 10 ) and promotes endothelial barrier function through elevation of intracellular cAMP ( 4 , 11 ). (jimmunol.org)
- 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)
- 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)
- Antagonizes the activity of NECA, an adenosine receptor agonist. (hellobio.com)
- The CellAura fluorescent adenosine A 3 antagonist [XAC] ligand was shown to antagonize the activity of the adenosine receptor agonist, NECA, in three separate recombinant CHO cell lines expressing the human A 1 , A 2A or A 3 receptor and a cyclic AMP-responsive secreted placental alkaline phosphatase (SPAP) reporter gene. (hellobio.com)
- To determine the apparent KD for CellAura fluorescent adenosine A 3 antagonist [XAC], cells were treated with varying concentrations of NECA alone, or in the presence of 1µM CellAura fluorescent adenosine A 3 antagonist [XAC], and the cyclic AMP-induced expression of SPAP measured. (hellobio.com)
- Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils. (wikipedia.org)
- For example, in the brain area for movement control (striatum), natural adenosine acting at postsynaptic A2A receptors generally suppresses movement. (grantome.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)
- In the central nervous system, the purine nucleoside adenosine has been implicated in beneficial and detrimental actions of morphine, but the extent of their interaction remains poorly understood. (bvsalud.org)
- Jacobson KA, Ji X-d, Li AH, Melman N, Siddiqui MA, Shin KJ, Marquez VE, Ravi RG (2000) Methanocarba analogues of purine nucleosides as potent and selective adenosine receptor agonists. (springer.com)
- Baranowski RL, Westenfelder C (1994) Estimation of renal interstitial adenosine and purine metabolites by microdialysis. (springer.com)
- Sajjadi FG, Firestein GS: cDNA cloning and sequence analysis of the human A3 adenosine receptor. (drugbank.ca)
- Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG: Molecular cloning and characterization of the human A3 adenosine receptor. (drugbank.ca)
- PMID 18583455 Tracey WR, Magee WP, Oleynek JJ, Hill RJ, Smith AH, Flynn DM, Knight DR. Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury. (wikipedia.org)
- Agonist activity at human Adenosine A1 receptor expressed in yeast cells coexpressed with chimeric GPA1/Galphai1 after 16 hrs by beta galactosidase r. (bindingdb.org)
- The objective of the present study was to investigate whether genetic manipulation of the cardiac myocyte, achieved by gene transfer and overexpression of the human A3 receptor cDNA, renders the myocytes resistant to the deleterious effect of ischemia. (garvan.org.au)
- 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)
- We report the induction and reduction of adenosine receptor A2a and A3 mRNAs, respectively, during maturation of human monocyte-derived dendritic cells. (nih.gov)
- In human skin explant culture experiments the emigration of epidermal and dermal dendritic cells was diminished by the addition of 5'-(N-ethylcarboxamido)-adenosine. (nih.gov)
- In a chemotaxis assay of human dendritic cells in response to macrophage inflammatory protein 3beta (MIP-3beta)/CCL19, adenosine caused a delay in transmigration. (nih.gov)
- Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. (biomedsearch.com)
- Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. (wikipathways.org)
- Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury. (wikipathways.org)
- 3'-Aminoadenosine-5'-uronamides: discovery of the first highly selective agonist at the human adenosine A3 receptor. (naver.com)
- The stimulation of human leukocytes by various agents such as calcium ionophores, soluble agonists, or phagocytic stimuli results in the biosynthesis of the bioactive arachidonic acid (AA)-derived leukotrienes (LTs). (aspetjournals.org)
- EC50 values are 1nM, 1.1μM and 2 μM for transactivation of human PPARδ, -α, and -γ receptors respectively. (bioll.com)
- The adenosine A 2B receptor , also known as ADORA2B , is a G-protein coupled adenosine receptor , and also denotes the human adenosine A 2b receptor gene which encodes it. (wikidoc.org)
- To examine the functional significance of this receptor expression, we applied a femoral artery injury model to A2bAR knockout (KO) mice and showed that the A2bAR prevents vascular lesion formation in an injury model that resembles human restenosis after angioplasty. (pnas.org)
- In the current study we examined the role of vascular and bone marrow adenosine receptors in vascular response to injury using a model that mimics human restenosis after angioplasty. (pnas.org)
- Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATP channel activation. (semanticscholar.org)
- Activation of adenosine A(3) receptors potentiates stimulatory effects of IL-3, SCF, and GM-CSF on mouse granulocyte-macrophage hematopoietic progenitor cells. (semanticscholar.org)
- Blockade of adenosine A2B receptors ameliorates murine colitis. (nih.gov)
- Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models. (springer.com)
- In a murine contact hypersensitivity assay 5'-(N-ethylcarboxamido)-adenosine caused a reduction in the numbers of epidermal and dermal dendritic cells arriving in the draining lymph node. (nih.gov)
- For instance, adenosine inhibits the proliferation of murine VSMC via activation of the A2bAR ( 4 ). (pnas.org)
- Implication for a role of cardiac P2X purinergic receptors. (springer.com)
- The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. (jove.com)
- Adenosine-dependent regulation of renal function in healthy and diseased kidney is mediated by activation of the four types of P1 purinergic adenosine receptors (A 1 AR, A 2A AR, A 2B AR, A 3 AR). (springer.com)
- Piclidenoson, "a novel, first-in-class, A3 adenosine receptor agonist small molecule, orally bioavailable drug," is said to offer safer and more effective oral treatment for canine osteoarthritis. (benzinga.com)
- RAD140 is a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). (bioll.com)
- Abebe W, Hussain T, Olanrewaju H et al (1995) Role of nitric oxide in adenosine receptor-mediated relaxation of porcine coronary artery. (springer.com)
- As a result, adenosine decreases the phagocytic activity of macrophages by suppressing the generation of nitric oxide (18), superoxide (19, 20) and pro-inflammatory cytokines (21). (deepdyve.com)
- IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis. (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)
- Here, we demonstrate that morphine-induced OIH and antinociceptive tolerance in rats is associated with a twofold increase in adenosine kinase (ADK) expression in the dorsal horn of the spinal cord. (bvsalud.org)
- Some surface receptors such as G-protein-coupled receptors represent another class of molecule that can be inhibited by small-molecule compounds. (biomedcentral.com)
- Activating the A3 receptor - either by its native chemical stimulator, the small molecule adenosine, or by synthetic small molecule drugs invented at the National Institutes of Health - prevents or reverses pain that develops slowly from nerve damage, according to researchers at the National Institute of Health and Saint Louis University. (psychcentral.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)
- The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. (biomedsearch.com)
- In a study published in the April 15, 2015 issue of the Journal of Neuroscience, Saint Louis University (SLU) scientists, led by Professor of Pharmacological and Physiological Sciences Daniela Salvemini, Ph.D., discovered that drugs targeting the A3 adenosine receptor can "turn off" pain signals in the spinal cord to provide relief from chronic pain. (bioquicknews.com)
- The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. (drugbank.ca)
- Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
- The extent to which this finding applies to other G protein-coupled receptors and their interaction with different G proteins is unknown. (aspetjournals.org)
- This was true even when the receptor was shown, in the same assay, to exist in two different conformational states coupled to two different G proteins. (aspetjournals.org)
- ERK1/2 and CREB signaling proteins, which are induced by the activation of G-protein coupled receptors (GPCRs), cause plasticity changes and inflammatory responses in the spinal nerves. (ekja.org)
- Novel peptidomimetic compounds are disclosed, compounds that inhibit protein-protein interactions (PPI) of epidermal growth factor receptors (EGFR), also called. (patents.com)
- Adenozinski A 3 receptori je G protein-spregnuti receptor koji učestvuje u mnogobrojnim ćelijskim signalnim putevima i fiziološkim funkcijama. (wikipedia.org)
- Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. (wikipedia.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)
- Furthermore, adenosine significantly attenuated protein degradation of A2A and A3 receptors induced by LPS. (physiology.org)
- In addition to plasma membrane G protein-coupled chemokine receptors, small molecules can be designed to block intracellular enzymes that control signaling pathways. (biomedcentral.com)
- cAMP NOMAD ADORA1 Cell Line allows to assay compounds analyzing the G-Protein signalling pathway by Go involving receptor activation. (innoprot.com)
- When an agonist binds to ADORA1, Go protein is activated which, in turn, triggers a cellular response mediated by cAMP. (innoprot.com)
- When an agonist binds to [ArgAVP, the Gs protein is activated which, in turn, triggers a cellular response mediated by cAMP via adenylate cyclase stimulation. (innoprot.com)
- The results of this study, obtained by using real time RT-PCR and Western blotting, show that adenosine is able to increase both MMP9 mRNA and protein levels through the activation of the A3 adenosine receptor. (unife.it)
- We also noted that the A3 receptor stimulation led to increased levels of MMP9 protein in cellular extracts of U87MG cells, through phosphorylation of ERK1 / 2, JNK, Akt / PKB and the transcription factor AP-1. (unife.it)
- This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. (wikidoc.org)
- We found an important role for this receptor in regulating lesion formation associated with an increased level of the progenitor-attracting protein CXCR4. (pnas.org)
- In these reviews we summarized the status of the art on the role of the A3 receptor in different types of immune cells including neutrophils, eosinophils, lymphocytes, monocytes, macrophages and dendritic cells. (unife.it)
- Recent studies have shown the presence of A3 receptors on neutrophils, which represent the majority of circulating leukocytes and are the first cells to be recruited into a site of tissue inflammation in defending the body against infection. (unife.it)
- TDI decreased the stimulation of lymphocyte c-Adenosine-monophosphate (cAMP) concentrations by the receptor agonists isoproterenol and prostaglandin-E1. (cdc.gov)
- In the rat isolated omental mast cell we conclude that degranulation is an indirect result of A 1 receptor stimulation. (hindawi.com)
- Finally, as for the physiological relevance of the A3 receptor-mediated stimulation of MMP-9 we found that the A3 agonist was responsible for an increase of the invasive ability of U87MG cells. (unife.it)
- Adenosine antagonises the effect of ATP by stimulation of adenosine receptors suppressing the pro-inflammatory response (14-17). (deepdyve.com)
- During episodes of inflammation, multiple cell types release adenine nucleotides in the form of ATP, ADP, 5′-AMP, and adenosine. (jimmunol.org)
- A3 receptor agonists and/or agonists may have important clinical value in the treatment of asthma and inflammation. (creative-bioarray.com)
- Awad AS, Huang L, Ye H et al (2006) Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy. (springer.com)
- In general, the A2-type receptors have been described as sensors of tissue damage during an immune response ( 2 ), and A2aARs have been described as having a nonredundant role in the attenuation of inflammation and tissue damage in vivo ( 3 ). (pnas.org)
- Adenosine receptors also play a major role in several inflammation-associated processes by inhibiting immune activation and preventing excessive tissue damage. (pnas.org)
- The relative potencies of agonists for the A2B adenosine receptor could only be tested by measurement of receptor-stimulated adenylyl cyclase activity. (biomedsearch.com)
- Indirect evidence suggests that the adenylyl cyclase stimulatory A2b adenosine receptors (A2bARs) also affect vascular function ( 4 - 6 ). (pnas.org)
- The A3 adenosine receptor agonist CP-532,903 [N6-(2,5-dichlorobenzyl)-3'-aminoadenosine-5'-N-methylcarboxamide] protects against myocardial ischemia/reperfusion injury via the sarcolemmal ATP-sensitive potassium channel. (wikipedia.org)
- In a mouse model of infarction the A3 selective agonist CP-532,903 protected against myocardial ischemia and reperfusion injury. (wikipedia.org)