Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Receptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Receptor, Adenosine A3: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Receptor, Adenosine A2B: A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Receptors, Adenosine A2: A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Serotonin 5-HT1 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.Xanthines: Purine bases found in body tissues and fluids and in some plants.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Serotonin 5-HT2 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).GABA-A Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.Receptors, Purinergic: Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.Serotonin 5-HT4 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.2-Chloroadenosine: 2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine: A selective D1 dopamine receptor agonist used primarily as a research tool.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Baclofen: A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Quinpirole: A dopamine D2/D3 receptor agonist.5'-Nucleotidase: A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.Nicotinic Agonists: Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.Receptors, Opioid, delta: A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.Receptors, Dopamine D1: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Inosine: A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)Piperidines: A family of hexahydropyridines.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Benzazepines: Compounds with BENZENE fused to AZEPINES.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.Enkephalin, Ala(2)-MePhe(4)-Gly(5)-: An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Cannabinoids: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Theobromine: 3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)Muscimol: A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.PyrrolidinesAdenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Adenine NucleotidesReceptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Triazines: Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.Purinergic P2Y Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.Kinetics: The rate dynamics in chemical or physical systems.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Receptors, Glucagon: Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.Benzoxazines: OXAZINES with a fused BENZENE ring.Purinergic P2X Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.Receptor, Cannabinoid, CB2: A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.Serotonin 5-HT3 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT3 RECEPTORS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Behavior, Animal: The observable response an animal makes to any situation.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Purinergic Agonists: Compounds that bind to and activate PURINERGIC RECEPTORS.PiperazinesColforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Mice, Inbred C57BLPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Receptors, Dopamine D3: A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.Ergolines: A series of structurally-related alkaloids that contain the ergoline backbone structure.Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Methylhistamines: Histamine substituted in any position with one or more methyl groups. Many of these are agonists for the H1, H2, or both histamine receptors.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Receptor, Serotonin, 5-HT1B: A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptors, Serotonin, 5-HT4: A subtype of G-protein-coupled SEROTONIN receptors that preferentially couple to GS STIMULATORY G-PROTEINS resulting in increased intracellular CYCLIC AMP. Several isoforms of the receptor exist due to ALTERNATIVE SPLICING of its mRNA.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.MorpholinesBenzeneacetamides: Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.Receptors, sigma: A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Receptors, Prostaglandin E: Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.TriazolesReceptor, Serotonin, 5-HT1A: A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Coformycin: A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.Receptors, Histamine: Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.Bicyclo CompoundsReceptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Receptors, Dopamine: Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Receptors, Histamine H3: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Bicyclo Compounds, Heterocyclic: A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Impromidine: A highly potent and specific histamine H2 receptor agonist. It has been used diagnostically as a gastric secretion indicator.Receptor, Serotonin, 5-HT2C: A serotonin receptor subtype found primarily in the CENTRAL NERVOUS SYSTEM and the CHOROID PLEXUS. This receptor subtype is believed to mediate the anorectic action of SEROTONIN, while selective antagonists of the 5-HT2C receptor appear to induce ANXIETY. Several isoforms of this receptor subtype exist, due to adenine deaminase editing of the receptor mRNA.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Receptors, Histamine H2: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Fenoldopam: A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Amphetamines: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Pentostatin: A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Hydrocarbons, FluorinatedAdenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Thioinosine: Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503)Adenosine Phosphosulfate: 5'-Adenylic acid, monoanhydride with sulfuric acid. The initial compound formed by the action of ATP sulfurylase on sulfate ions after sulfate uptake. Synonyms: adenosine sulfatophosphate; APS.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.QuinoxalinesPertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Dronabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Cyclohexanols: Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Receptors, Serotonin, 5-HT1: A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.
(1/77) Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury.

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)

(2/77) An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation.

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)

(3/77) Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced protection from cardiac ischemia.

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)

(4/77) Partial agonists for A(3) adenosine receptors.

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)

(5/77) Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes.

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)

(6/77) Activation of A3 adenosine receptors attenuates lung injury after in vivo reperfusion.

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)

(7/77) Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury.

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)

(8/77) CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic effect of 5-fluorouracil in a colon carcinoma murine model.

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)

*  Adenosine receptor
Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in ... The role of A3 receptor is less defined in this field. Studies have shown that it plays a role in the downregulation of ... The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as endogenous ... Br J Pharmacol 170(6):1167-1176 "Entrez Gene: ADORA2A adenosine A2A receptor". Jacobson KA, Gao ZG (2006). "Adenosine receptors ...
*  Adenosine A2A receptor
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 ...
*  Adenosine A3 receptor
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... 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". ...
*  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. ...
*  PSB-10
... 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, ...
*  Adenosine A2B receptor
"The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". J. Biol. Chem ... 2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". J. Comp ... The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human ... alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting ...
*  Caffeine-induced anxiety disorder
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors ... 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 ...
*  Adenosine
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 ...
*  Multiple electrode aggregometry
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- ...
*  Theophylline
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...
*  Purinergic signalling
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 ...
*  Valerian (herb)
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. ...
*  Adenosine diphosphate receptor inhibitor
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 ...
*  Methoctramine
... such as nicotinic ACh receptors -at micromolar concentrations- or adenosine A3. The exact effects of methoctramine still remain ... and other agonists, such as bethanechol or berberine). At higher concentrations, allosteric properties of methoctramine have ... Gallamine triethiodide M2 receptor Muscarinic receptor Acetylcholine Jakubik, Jan; Zimcik, Pavel; Randakova, Alena; Fuksova, ... As shown in the chart above, methoctramine binds preferently to M2 receptors, found mostly in the parasympathetic nerves and ...
*  Photoactivatable probes
Link, K.H.; Cruz, F.G.; Ye, H.F.; O'reilly, K.E.; Dowdell, S.; Koh, J.T. (2004). "Photo-caged agonists of the nuclear receptors ... "The E1 mechanism in photo-induced beta-elimination reactions for green-to-red conversion of fluorescent proteins". Chem Biol. ... Kaplan, J. H.; Forbush, B.; Hoffman, J. F. (1978). "Rapid photolytic release of adenosine 5'-triphosphate from a protected ... derivates of estradiol were shown to induce gene expression upon uncaging other caged hormones were used to study receptor - ...
*  Adrenergic receptor
... a Gq coupled receptor) and α2 (a Gi coupled receptor). Phenylephrine is a selective agonist of the α receptor. β receptors have ... 81 (1): 211.e1-7. doi:10.1016/j.urology.2012.09.011. PMID 23200975. Fitzpatrick D, Purves D, Augustine G (2004). "Table 20:2". ... "Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway ... Basic Neurochemistry: α- and β-Adrenergic Receptors Brief overview of functions of the β3 receptor Theory of receptor ...
*  Prostaglandin EP3 receptor
EP3 receptor-deficient mice and/or wild type mice treated with an EP3 receptor agonist are similarly protected from allergic ... Prostaglandin E1 (PGE1), which has one less double bond than PGE2, has the same binding affinity and potency for EP3 as PGE2. ... and pathways that inhibit adenyl cyclase which thereby lowers cellular levels of cyclic adenosine monophosphate (cAMP) to ... Eicosanoid receptor Prostaglandin E2 receptor 1 (EP1) Prostaglandin E2 receptor 2 (EP2) Prostaglandin E2 receptor 4 (EP4) ...
*  History of catecholamine research
... β2 and β3 and the five dopamine receptors D1, D2, D3, D4 und D5. Their fine structure, without agonist or agonist-activated, is ... A. Vulpian (1856). "Note sur quelques réactions propres à la substance des capsules surrénales". Comptes Rendus de l'Académie ... In addition the vesicles contained adenosine triphosphate (ATP), with a molar noradrenaline:ATP ratio in sympathetic nerve ... he called alpha adrenotropic receptor (now α-adrenoceptor or α-adrenergic receptor), while the receptor with the second rank ...
*  Arachidonate 5-lipoxygenase
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 ... may serve as a mobile lid over ALOX5's substrate-binding site An Adenosine triphosphate (ATP) binding site; ATP is crucial for ... Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ...
*  Cannabinoid receptor type 1
Endogenous CB1 antagonist and CB2 agonist) Rimonabant Taranabant Lipoxin A4 - endogenous, PAM ZCZ-011 - PAM Pregnenolone - ... Through its primary action as a Gi coupled receptor, CB1 inhibits production of cyclic adenosine monophosphate (cAMP), ... Repeated administration of receptor agonists may result in receptor internalization and/ or a reduction in receptor protein ... Selective CB1 agonists may be used to isolate the effects of the receptor from the CB2 receptor, as most cannabinoids and ...
*  Cannabinoid receptor type 2
CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP). Although the ... 11: e3. doi:10.1017/S1462399409000957. PMC 2768535 . PMID 19152719. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, ... The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or ... Unlike the CB1 receptor, in the brain, CB2 receptors are found primarily on microglia. The CB2 receptor is expressed in some ...
*  Parathyroid hormone 1 receptor
"Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by ... "Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: ... "Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related ... It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by Gs G ...
*  12-Hydroxyheptadecatrienoic acid
... subsequent studies showed that it was a high affinity receptor for the arachidonic acid metabolite, lipoxin A4, but also bound ... Syntheic BLT2 agonists may be useful for speeding the healing of chronic ulcerative wounds, particularly in patients with, for ... to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine ... BLT1 receptor) and its low affinity BLT2 receptor (Kd=23 nM); both receptors are G protein coupled receptors that, when ligand- ...
*  Caffeine
"Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer ... Caffeine is an antagonist at all four adenosine receptor subtypes (A1, A2A, A2B, and A3), although with varying potencies. The ... this is a receptor complex with 1 adenosine A1 receptor and 1 dopamine D1 receptor) and the A2A-D2 receptor heterotetramer ( ... this is a receptor complex with 2 adenosine A2A receptors and 2 dopamine D2 receptors). The A2A-D2 receptor heterotetramer has ...
*  Beta-2 adrenergic receptor
Alpha-2 adrenergic receptor Beta-1 adrenergic receptor Beta-3 adrenergic receptor Discovery and development of beta2 agonists ... 81 (1): 211.e1-7. doi:10.1016/j.urology.2012.09.011. PMID 23200975. Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill ... catalysing the formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A, and counterbalancing ... Identification of a conserved aspartate residue involved in agonist binding and receptor activation". The Journal of Biological ...
*  Cannabidiol
It has also been shown to act as a 5-HT1A receptor partial agonist, and this action may be involved in the antidepressant, ... is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A2A receptor. ... "Cannabis à faible teneur en THC et CBD". bag.admin.ch. Retrieved May 20, 2017. ... French and Spanish versions wrongly mention agonist action of CBD on cannabinoid receptors while the English version says CBD ...
A relationship between adenosine and the cardiac hormone ANP is not fully studied despite the existence of adenosine receptors and their effects in the heart. Our study has revealed that adenosine increases an ANP release with negative inotropism via stimulation of A1 receptor subtype and that cellular cAMP level regulates the ANP release.. Adenosine is well known as a physiological regulator of tissue function by increasing the energy supply and decreasing the energy demand. Adenosine also exerts a protective role against ischemic injury. In addition to cardioprotective effects, adenosine inhibits a release of vasopressor hormones. These hormonal effects may be expected to exert beneficial effects on the overloaded heart. We found that adenosine increases the ANP release directly from beating atria with negative inotropism. Our results agree with other reports that adenosine increases plasma concentration of ANP in vivo9,10 and in vitro experiments.11 Elias et al9 found a marked increase in ...
DESCRIPTION: (Adapted from the Investigators Abstract): Adenosine administered as an aerosol to asthmatics causes bronchoconstriction, while in non-asthmatics adenosine causes bronchodilation. This occurs because the activation of A2B adenosine receptors on sensitized mast cells triggers degranulation, releasing histamine, leukotrienes, and other allergic mediators. A2B adenosine receptors are blocked by theophylline, a xanthine that is effective in treating asthma. However, theophylline is a non-selective antagonist of all four adenosine receptor subtypes and produces side effects due primarily to A1 receptor blockade, including insomnia and diuresis. The incidence of asthma is increasing and current treatment options are limited. New drugs that are potent and selective antagonists of A2B adenosine receptors have great potential for the treatment of asthma and other allergic diseases. Adenosine Therapeutics, LLC owns the first potent and selective A2B antagonists. The purpose of this phase I ...
Objectives:. The overall goal of this proposal is to develop methods to achieve heart and vascular protection from ischemia and thus improve soldiers performance in adverse environment. The major hypothesis is that new approach and method can be developed to enhance resistance to stress-induced circulatory insufficiency and myocardial ischemia. The goals here are to determine whether a decreased adenosine transporter function is associated with a reduced physiological responsiveness to the vasculo-protective drug persantine using two in vitro endpoints: the ability of persantine 1) to inhibit platelet aggregation and 2) to inhibit [3H] uridine uptake. Both are endpoints that indicate physiological responsiveness. Both relate directly to the cardiovascular protective effects of , that is, persantine the availability of extracellular adenosine level and the anti-platelet property. Specifically, the relationship between circulating adenosine increase to persantine in vivo and blockade of ...
Adenosine is a candidate sleep substance. It can be both a distress signal of importance in pathology and a physiological regulator. Key factors in determining which of these possibilities pertain are: (i) the number of receptors expressed, and (ii) the mechanisms that establish extracellular adenosine levels. The roles of adenosine are studied by means of antagonists and/or animals (mostly mice) with targeted deletions of receptors or enzymes involved in adenosine metabolism. Whereas adaptive changes in the genetically modified mice can occur for the physiologically important effects, such adaptive changes are less likely to occur in situations where adenosine acts as a distress signal. The relevance to sleep will be covered only in general terms in this review and will be covered in other contributions to this volume.
Adenosine is 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. For instance, adenosine plays an important role in energy transfer - as adenosine triphosphate (ATP) and adenosine diphosphate (ADP). It also plays a role in signal transduction as cyclic adenosine monophosphate, cAMP. Adenosine itself is both a neurotransmitter and potent vasodilator. When administered intravenously, adenosine causes transient heart block in the AV node. Because of the effects of adenosine on AV node-dependent supraventricular tachycardia, adenosine is considered a class V antiarrhythmic agent ...
Previous in vitro studies have shown biphasic effects of adenosine on mast cell activity; however, the receptor subtypes that mediate the inhibitory effects of adenosine are still controversial (Peachell et al., 1991; Yip et al., 2009). Mast cells express two distinct Gs-coupled adenosine receptors; their biologic roles have not been comprehensively defined, especially in vivo. Since activation of Gs-coupled adenosine receptors increases intracellular cAMP, we hypothesized that the inhibitory effects of adenosine on mast cells are mediated by the Gs-coupled adenosine receptors. In this study, we used both genetically modified animal models and mast cell cultures to comprehensively investigate the role of Gs-coupled adenosine receptors on mast cells both in vitro and in vivo. First, our data demonstrate a potent inhibitory effect of the nonhydrolyzable adenosine analog NECA on IgE-induced mast cell degranulation; this inhibitory effect of NECA was abolished by the genetic deletion of the A2B but ...
Having the ability to modulate lymphocyte entry into the central nervous system (CNS) would benefit patients with neuroinflammatory diseases. We have previously shown that extracellular adenosine regulates CNS entry of lymphocytes during experimental autoimmune encephalomyelitis (EAE), the animal model for the CNS inflammatory disease multiple sclerosis. For instance, while extracellular adenosine levels are vastly increased following inflammatory cellular damage (from the hydrolysis of released cytoplasimic ATP by CD39 and CD73), mice lacking CD73 or given adenosine receptor (AR) antagonists have significantly reduced CNS lymphocyte entry during EAE. We now show through detailed genetic studies that AR signaling regulates lymphocyte migration into the CNS though induction of CX3CL1, a specialized chemokine that acts as both an adhesion molecule and chemoattractant for lymphocytes, monocytes, and NK cells. We show that AR signaling is necessary and sufficient to induce CNS expression of CX3CL1 ...
The double-blind, placebo-controlled study looked at 40 healthy male subjects who were randomized to receive ticagrelor (180 mg) or placebo. Results showed that ticagrelor significantly increased the area under the curve of CBFV vs. the adenosine dose compared with placebo (p = 0.008). There was a significant correlation between ticagrelor plasma concentrations and increases in the area under the curve (p , 0.001). In both treatment groups, the adenosine-induced increase in CBFV was significantly attenuated by theophylline, with no significant differences between subjects receiving ticagrelor or placebo (p = 0.39). Furthermore, ticagrelor significantly enhanced the sensation of dyspnea during adenosine infusion, and the effects were diminished by theophylline. As previous studies have shown ticagrelor significantly and dose dependently augmented adenosine-meditated coronary blood flow increases in a dog model, the study authors note that their study showed "that ticagrelor augments ...
Vasodilator stress with adenosine or dipyridamole is an alternative to exercise stress with myocardial perfusion imaging for the detection of coronary artery disease. Although the safety of adenosine and dipyridamole has been well established, undesirable side effects including chest pain, headache, dyspnea, and atrioventricular conduction abnormalities do occur in a majority of patients.1-4 In addition, both adenosine and dipyridamole produce severe bronchoconstriction when given to asthmatics. Because of its ultrashort half-life, adenosine must be administered by a constant IV infusion.. Whereas adenosine-induced coronary vasodilatation is mediated primarily by stimulation of the A2A receptor subtype on vascular smooth muscle, the side effects described above are believed to be caused by stimulation of 1 or more of the other 3 adenosine receptor subtypes, A1, A2B, and A3.5 The discovery of highly selective and relatively short-acting adenosine receptor A2A agonists6-9 has opened the ...
A concise synthesis of a series of N6-substituted adenosines with bicyclo[3.2.1]octan-6-yl and polycyclic N6-substituents has been developed. The adenosine A1 receptor (A1R) affinity and potency of these compounds was initially assessed using competitive binding assays and cyclic adenosine monophosphate (cAMP) accumulation assays in DDT1 MF-2 cells. The potency and receptor subtype selectivity of selected examples was further evaluated by measuring their effects on cAMP accumulation at all human adenosine receptor subtypes expressed in CHO cells. The results of these assays indicated that all of the synthesised N6-substituted adenosines are full agonists at A1R and activate this receptor selectively over the other adenosine receptor subtypes. The two standout compounds in terms of potency were N6-(3-thiabicyclo[3.2.1]octan-6-yl)adenosine and N6-(cubanylmethyl)adenosine with EC50 values at human A1R of 2.3 nM and 1.1 nM, respectively. The cubanylmethyl derivative in particular proved to be highly ...
We examined how the endogenous anticonvulsant adenosine might influence gamma-aminobutyric acid type A (GABA(A)) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current (I(GABA)) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced I(GABA) run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in approximately 40% and approximately 20% of tested oocytes, respectively. The ...
Introduction: Prior studies demonstrate that ischemic preconditioning (IP) alters adenosine metabolism. The significance of this effect is not fully understood, but evidence suggests that reduction in extracellular adenosine may represent use as an alternative fuel. Transformation into AMP/ADP may also replenish intracellular total adenine nucleotides (TAN), improving the potential high-energy phosphate bonds available in cells facing ischemia. In both cases, adenosine supports cell energy requirements and may be a key component of IPs protective mechanisms. There are no previous studies of brain adenosine in human patients undergoing remote IP.. Methods: In adults with aneurysmal subarachnoid hemorrhage (SAH), 3-4 remote IP sessions were conducted on non-consecutive days, 4-12 days after hemorrhage. Each session consisted of 4 5-min cycles of lower extremity blood pressure cuff inflation to 30mmHg above systolic blood pressure, followed by 5-min reperfusion. Patients had microdialysis (MD) ...
Adenosine deaminase (ADA) is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues. Present in virtually all mammalian cells, its primary function in humans is the development and maintenance of the immune system. Adenosine deaminase is considered one of the key enzymes of purine metabolism. Adenosine deaminase in humans is involved in the development and maintenance of the immune system. However, Adenosine deaminase association has also been observed with epithelial cell differentiation, neurotransmission, and gestation maintenance. It has also been proposed that Adenosine deaminase, in addition to adenosine breakdown, stimulates release of excitatory amino acids and is necessary to the coupling of A1 adenosine receptors and heterotrimeric G proteins.. ...
A review. The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain G protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various species, including rat and human, and its sequences are highly similar across species, ranging from 85% identity between human and mouse and 95% identity between rat and mouse. The A2B receptors show a ubiquitous distribution, the highest levels are present in cecum, colon and bladder, followed by blood vessels, lung, eye and mast cells. Through A2B receptors adenosine seems to cause mast cells degranulation, vasodilation, cardiac fibroblast proliferation, inhibition of Tumor Necrosis Factor (TNF-α), increased synthesis of interleukin-6 (IL-6), stimulation of Cl- secretion in intestinal epithelia and hepatic glucose prodn. Hence, A2B adenosine receptor agonists could be useful ...
It is generally accepted that the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) arises mainly from the inhibition of cyclooxygenase (COX). However, more evidence has suggested that certain pharmacological actions of NSAIDs may be mediated by COX-independent mechanisms. The present study investigated the effects of NSAIDs on adenosine uptake in human aortic smooth muscle cells (HASMCs). Among the NSAIDs tested (all at 100 µM), aspirin, ibuprofen and naproxen had no effect on [3H]adenosine uptake. Piroxicam inhibited [3H]adenosine uptake by 30%, while etodolac, indomethacin, ketoprofen, mefenamic acid and sulindac inhibited [3H]adenosine by 13-18%. Sulindac sulfide, an active metabolite of sulindac, inhibited [3H]adenosine uptake and [3H]nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding of HASMCs with IC50 values of 40.67 ± 4.82 and 24.19 ± 3.76 μM, respectively. Kinetic studies revealed that sulindac sulfide was a competitive inhibitor of adenosine uptake. Using the
The effect of (-)-N6-phenylisopropyl adenosine (PIA), a metabolically stable P1-receptor agonist, was investigated on guinea-pig isolated trachea. PIA showed two opposite effects: contraction, evident at low concentrations (10(-7) to 2-5 X 10(-6) M), and relaxation at higher doses. Relaxation by PIA was antagonized in an apparently competitive manner by two antagonists of extracellular (P1) adenosine receptors: theophylline (Theo) and 8-phenyltheophylline (PT). Contraction by PIA was not inhibited by methylxanthines and was not mediated by stimulation of cholinergic or histaminergic systems. Inhibitors of arachidonic acid cascade acting at different levels, i.e. indomethacin, nordihydroguaiaretic acid (NDGA) and BW755C, all inhibited the contraction by PIA, while they potentiated the relaxation in a concentration-dependent manner. Mepacrine, an inhibitor of phospholipase A2, inhibited the contraction by PIA, but did not affect the relaxation. These results indicate that the contractile effect induced by
Adenosine is a purine nucleoside that is commonly expressed in the body and involved in a wide range of physiological processes. The effects of adenosine are mediated through specific G-protein coupled cell surface receptors, named A1, A2A, A2B and A3 adenosine receptors (ARs). It is now well recognized that extracellular levels of adenosine markedly increase under metabolically stressful conditions and in the last two decades it has become clear that adenosine is a mediator involved in the pathogenesis of lung inflammatory disorders and in cancer. Indeed adenosine induces bronchoconstriction in animal models and in patients with airway diseases such as asthma and chronic obstructive pulmonary diseases (COPD). COPD is defined as an inflammatory respiratory disease, largely caused by exposure to tobacco smoke. The disease is characterized by a progressive and incompletely reversible airflow obstruction. The key elements of COPD are exposure to cigarette smoke, airway inflammation, and airflow ...
Pharmacologic stress with dipyridamole has provided useful diagnostic, as well as prognostic, information in patients undergoing thallium-201 myocardial perfusion imaging. With its ultrashort half-life and a potent and consistent vasodilator effect, adenosine may be the coronary vasodilator of choice with myocardial perfusion imaging.. Fifty-one healthy subjects and 93 patients with suspected coronary artery disease constituted the study group. In this multicenter study the comparative safety and diagnostic efficacy of single-photon emission computed tomography (SPECT) thallium imaging during adenosine-induced coronary hyperemia was compared with exercise treadmill stress. There was a mean increase in heart rate of 37% and a mean decrease in diastolic blood pressure of 5% during the adenosine infusion of 140 μg/kg per min for 6 min. Adenosine infusion was well tolerated in 95% of the subjects. Side effects requiring intervention occurred in seven subjects (5%). None of the subjects experienced ...
BioAssay record AID 33566 submitted by ChEMBL: Inhibition of [3H]5-(N-ethylcarbamoyl)-adenosine binding to adenosine A2 receptor in rat striatal membranes with 50 nM cyclopentyladenosine.
... | Antiviral Therapy | 2007 Feb; 12(6):853-63 Nucleoside transporter proteins (NTs) encoded by members of the SLC28 and SLC29 gene families contribute to nucleoside and nucleobase recycling but also modulate extracellular adenosine levels and thus adenosine-regulated metabolic targets. Methods: We have examined…
Looking for online definition of cyclic adenosine monophosphate (cyclic AMP, cAMP, 3',5'-cAMP) in the Medical Dictionary? cyclic adenosine monophosphate (cyclic AMP, cAMP, 3',5'-cAMP) explanation free. What is cyclic adenosine monophosphate (cyclic AMP, cAMP, 3',5'-cAMP)? Meaning of cyclic adenosine monophosphate (cyclic AMP, cAMP, 3',5'-cAMP) medical term. What does cyclic adenosine monophosphate (cyclic AMP, cAMP, 3',5'-cAMP) mean?
Adenosine monophosphate deaminase deficiency type 1, also called myoadenylate deaminase deficiency (MADD), is a recessive genetic metabolic disorder that affects approximately 1-2% of populations of European descent. It appears to be considerably rarer in Asian populations. The genetic form is caused by a defect in the gene for AMP deaminase though there is also an acquired form of AMP deficiency. Although many people with a defective AMPD gene are asymptomatic, others may have symptoms such as exercise intolerance, muscle pain, and muscle cramping. Fatigue MADD lowers aerobic power output, so increased anaerobic power is needed to perform the same amount of work.[citation needed] Without myoadenlyate deaminase, heavy activity causes adenosine to be released into the cell or perfused into the surrounding tissues. Fatigue and sedation after heavy exertion can be caused by excess adenosine in the cells which signals muscle fiber to feel fatigued. In the brain, excess adenosine decreases alertness ...
Purpose: : Traumatic optic neuropathy (TON) is an irreversible vision-threatening complication often found in head injuries. Following optic nerve trauma, the bodys innate immune cells scavenge the trauma site for debris while releasing cytokines that cause additional damage and cell death beyond that of the initial insult. While neuronal cell loss stemming directly from the initial insult is irreversible, the secondary inflammation from cytokine release may be prevented. The purpose of our study is to further elucidate mechanisms by which exogenous agonists can effect anti-inflammation and ultimately curb the damage from TON before it is irreversible. Under stress or ischemia such as TON, local tissue concentrations of adenosine are likely to increase due to the release of ATP and its conversion to adenosine by ectonucleotidases including CD73. The released adenosine is anti-inflammatory, as seen in other organ systems, by stimulating the adenosine receptor A2AAR. We tested the hypothesis that ...
Synonyms for adenosine deaminase conjugated with polyethylene glycol in Free Thesaurus. Antonyms for adenosine deaminase conjugated with polyethylene glycol. 2 words related to adenosine: biochemistry, nucleoside. What are synonyms for adenosine deaminase conjugated with polyethylene glycol?
Concordant with data derived from A2A-null CD4+/CD25− (Fig. 4 D), proliferation responses of CD4+/CD25− T cells obtained from Cd39-null mice are exaggerated after 6 d of stimulation, which is coincident with the up-regulation of adenosine receptor A2A in CD4+/CD25− cells (Fig. 5 C). As a further confirmation of direct connections between CD39 expression and adenosine generation, effects of the addition of soluble exogenous NTPDases (apyrase grade VII) to Cd39-null T cell cultures were tested. This reconstitution effectively suppresses the abnormal proliferation of CD4+/CD25− cells (Fig. 5 C) and restores anergy within the T reg cell pool (not depicted).. We next examined the suppressive ability of WT and Cd39-null T reg cells to inhibit the proliferation of WT or Cd39-null effector cells, respectively. An in vitro system was chosen whereby effector cells were activated with anti-CD3 and anti-CD28. This system was chosen to eliminate the expression of CD39 on stimulating cells, which ...
The uroepithelium lines the urinary bladder, urethra and the lower renal pelvis. It provides a tight blood-urine barrier that prevents the unregulated movement of solutes, ions and metabolites present in the urine. Apart from forming a robust barrier, a growing body of evidence supports the role of the uroepithelium as a sensory transducer that is sensitive to extracellular biochemical and mechanical stimuli. One of the mediators that is released from the uroepithelium and impacts bladder activity is adenosine. Adenosine is a well-known stress relieving hormone in other organ systems and the bladder lumen is a region of constant stress due to cyclical filling and voiding of urine, therefore I hypothesized that adenosine has an impact on urinary bladder function under stress. First I assessed the mechanism of adenosine turnover and how luminal adenosine affects bladder function. I report that adenosine is released from the mucosal and serosal surfaces of the uroepithelium when the tissue is ...
TY - JOUR. T1 - Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2-deoxycoformycin. AU - Hershfield, M. S.. AU - Kurtzberg, J.. AU - Harden, E.. AU - Moore, J. O.. AU - Whang-Peng, J.. AU - Haynes, B. F.. PY - 1984/3/22. Y1 - 1984/3/22. N2 - Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpectedly, within 7 days of starting treatment, the leukemic phenotype underwent complete conversion from T lymphoblastic to promyelocytic, with kinetics that suggested a precursor-product relationship between the two cell populations. Pretreatment of T lymphoblasts and posttreatment of promyelocytes had the same abnormal karyotype. Upon culture in vitro, the former transformed spontaneously over several weeks into mature myeloid cells. We ...
We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2 , 200 mm Hg; group II PaO2 = 50 mm Hg; and group III: PaO2 = 100 mm Hg. We treated a fourth group whose PaO2 = 100 mm Hg with phentolamine to block the 44% rise in blood pressure which occurred with the onset of seizures. PaCO2 was maintained between 30 anf 40 mm Hg in all groups. Brain tissue was sampled rapidly after 0, 10, 20, 30, 60, and 120 seconds of seizures by the freeze-blow technique. With normoxia (PaO2 = 100 mm Hg) or hyperoxia (PaO2 , 200 mm Hg), adenosine increased within ten seconds of the onset of seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A ...
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Exogenous administration of adenosine induces atrial fibrillation in up to 7.0% of patients. Animal studies affirm endogenous adenosine released in response to tissue hypoxia may play a mechanistic role in arrhythmias associated with myocardial ischaemia or hypoxia. Therefore, atrial fibrillation occurring early after the acute phase of myocardial infarction involving atrial tissue may be secondary to an excessive accumulation of adenosine that leads to a shortening of atrial refractory period. Early in the course of acute inferior myocardial infarction, two patients (males aged 45 and 68) suffered new onset sustained atrial fibrillation that was abrupt in onset and complicated their clinical management. They were administered 250 mg theophylline as a slow intravenous injection at a rate of 100 mg/min or until conversion to normal sinus rhythm occurred. Both patients converted to normal sinus rhythm within five minutes of the administration of theophylline. In up to 52 hours of continuous ECG ...
RNA Editing is a type of post-transcriptional modification that takes place in eukaryotes. It alters the sequence of primary RNA transcripts by deleting, inserting or modifying residues. Several forms of RNA editing have been discovered including A-to-I, C-to-U, U-to-C and G-to-A. Here we focus on A-to-I editing (Adenosine-to-Inosine), the most frequent and common one [1]. Adenosine (A) deamination produces its conversion into inosine (I), which, in turn, is interpreted by both the translation machinery and the splicing machinery [2] as guanosine (G). Since inosine binds cytosine (C), the A-U base pairs in the secondary structure are changed into I:U mismatches [3]. This biological phenomenon is catalyzed by enzymes members of the Adenosine Deaminase Acting on RNA (ADAR) family and occurs only on dsRNA structures [1, 4, 5].. The A-to-I RNA editing may be either promiscuous or specific. The promiscuous RNA editing occurs within long duplexes [6, 7], while specific RNA editing A-to-I occurs within ...
Hereditary hemolytic anemia, a dominantly transmitted disorder, has affected 12 family members spanning three generations. The concentration of adenosine triphosphate in the red cells was about half that of comparably reticulocyte-rich blood. Since adenosine deaminase and adenosine kinase compete for a common substrate, the greatly increased activity of the former may interfere with nucleotide salvage via the latter. ...
Adenosine uptake via nucleoside transporters is inhibited when S49 and NG108-15 cell lines cells are exposed to ethanol. This inhibition leads to an accumulation of extracellular adenosine that binds to adenosine A2 receptors and increases cAMP production. Subsequently, there is a heterologous desensitization of receptors coupled to adenylyl cyclase for which adenosine also is required. There are multiple classes of facilitative and concentrative nucleoside transporters that could be inhibited by ethanol to initiate this cascade of events. In this paper, we establish that adenosine uptake by only one type of nucleoside transporter, an NBMPR-sensitive facilitative transporter, is inhibited by ethanol. There is no effect on other classes of nucleoside transporters even when present in the same cell. Thus, ethanol-induced extracellular accumulation of adenosine results specifically from inhibition of NBMPR-sensitive facilitative nucleoside transporters. We also find that human lymphocytes express ...
In collaboration with Dr. Tarja Porkka-Heiskanen, we tested the role of nitric oxide (NO) in sleep homeostasis by using in vivo microdialysis to administer compounds into the rat basal forebrain that increase or decrease concentrations of NO. Consistent with our hypothesis, we found that nitric oxide production is required for the production of NREM recovery sleep following sleep deprivation. However, using specific inhibitors of nitric oxide synthases, we found that iNOS rather than nNOS produced the nitric oxide involved in homeostatic sleep regulation. The generation of NREM recovery sleep was tightly associated with increases in adenosine levels in the BF: when adenosine concentration was not elevated, recovery sleep was not induced while all cases of recovery sleep induction were preceded by adenosine increases. These results suggest that the elevation of NO in the BF during prolonged wakefulness is a specific mechanism for producing NREM recovery sleep. We are now interested in the ...
To evaluate the clinical and laboratory characteristics of pleural effusions in to tuberculosis (TB) or cancer (CA). A total of 385 patients with pleural effusion due to TB (n=175) or CA (n=112) were studied. The following parameters were analyzed: patient gender, age and pleural effusion characteristics (size, location, microscopic fluid aspect protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase activity (ADA) and nucleated cell counts).. Key words:. Pleural effusion. Neoplasm. Tuberculosis. Carcinoma. Adenosine deaminase. Patients, Lactate dehydrogenase. Exudates, Transudate.. The objective of this study was to evaluate the utility of the determination of protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE). We retrospect tively reviewed the clinical records of 385 patients with pleural effusion and investigated ...
Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines such as I are prepd. as selective adenosine A2a and A3 receptor antagonists. Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines substituted at the 9-position retain receptor affinity but lose selectivity for the adenosine A2a and A3 receptors over other adenosine receptors. Replacement of the furan moiety present in the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine with a Ph or a substituted arom. ring abolishes affinity at all the adenosine receptor subtypes, demonstrating that the furanyl ring is a necessary structural element to guarantee interaction with the adenosine receptor surface; replacement of the furan ring with an ortho-ethoxy-substituted arom. ring did not enhance affinity. Introduction of a N-methylpiperazinomethyl or morpholinomethyl function at the 5 position of the furanyl ring of I or introduction of a methylsulfanyl moiety at the 9-position of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines yields inhibitors with improved ...
Curr Top Med Chem 11:1034-1046 Squadrito F, Bitto A, Altavilla D et al (2014) The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial. J Clin Endocrinol Metab 99:E746-E753 Storr M, Thammer J, Dunkel R et al (2002) Modulatory effect of adenosine receptors on the ascending and descending neural reflex responses of rat ileum. BMC Neurosci 3:21 Sullivan GW, Rieger JM, Scheld WM et al (2001) Cyclic AMP-dependent inhibition of human neutrophil oxidative activity by substituted 2-propynylcyclohexyl adenosine A(2A) receptor agonists. Am J Physiol Renal Physiol 290(4):F828-837 Baldwin SA, Beal PR, Yao SY et al (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447:735-743 Belardinelli L, Shryock JC, Snowdy S et al (1998) The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther 284:1066-1073 Biber K, Klotz KN, Berger M et al (1997) Adenosine A1 receptor-mediated activation of ...
Incubation of human erythrocytes in medium containing inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) at pH 6.6 leads to a more than 1000-fold increase in the concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP), as identified and quantified by 31P-n.m.r. spectroscopy. The accumulation is highly pH-dependent, with a maximum at extracellular pH 6.60, and the maximum value of 1.3-1.6 mmol/l of erythrocytes is attained within 1 h at 37 degrees C. PRPP was accumulated despite high concentrations of 2,3-bisphosphoglycerate (2,3-BPG), an inhibitor of PRPP synthetase. The concentration of PRPP correlated with the intracellular concentration of inorganic phosphate (Pi). Substitution of either adenosine or adenosine plus inosine for inosine in the medium did not lead to 31P-n.m.r.-detectable accumulation of PRPP. These results show that neither 2,3-BPG nor PRPP itself inhibits the synthesis of PRPP in the human erythrocyte. Adenosine, however, prevents the inosine-stimulated ...
article{2286a0f7-5934-41f8-aed8-94b7a8b75a40, abstract = {Recent studies indicate a severely reduced coronary flow reserve (CFR) in neonates with congenital heart disease. The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown. This study was designed to establish normal values for CFR in newborns after administration of adenosine [pharmacologic CFR (pCFR)] and as induced by acute hypoxemia (reactive CFR). Thirteen mechanically ventilated newborn lambs were studied. Coronary flow velocities were measured in the proximal left anterior descending coronary artery before and after adenosine injection (140 and 280 mug/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (Sao(2)) and during progressive hypoxemia induced by lowering the fraction of inspired oxygen. CFR was defined as the ratio of hyperemic to basal average peak flow velocity. In ...
Perspective: Systemic right ventricles are at high risk of contractile dysfunction, the cause of which is still unclear. The chronic exposure of the morphological right ventricle to systemic pressure leads to significant hypertrophy. Ischaemia has been postulated to contribute to the right ventricular systolic dysfunction by a number of mechanisms. Supply demand mismatch from an inadequate coronary circulation to support the hypertrophied right ventricle may contribute. In addition, systemic arterial hypoxaemia in the preoperative period and the cardiopulmonary bypass for correction may damage the RV myocardium1, 2, 3. Small numbers of paediatric and adult patients with systemic right ventricles have been studied using myocardial perfusion single photon emission tomography (SPECT) with Sestamibi. A variety of fixed and inducible perfusion defects have been described and believed to be associated with the degree of right ventricular dysfunction and the delay to corrective surgery 2, 3. Myocardial ...
Methods Thirty-two male Sprague-Dawley rats (310-360 g) were anaesthetised and divided into four equal groups (n=8 each): Saline, Saline+MA, Theophylline, and Theophylline+MA. In the two MA groups, the sparrow-pecking MA technique was applied at 30 repetitions per min for 1 min to a depth of 15-18 mm using a stainless steel acupuncture needle (0.20×40 mm). The stimulus point was located on the right tibialis anterior (TA) muscle 7-8 mm below the knee. Animals in the two theophylline groups were intra-arterially injected with 8-(p-sulphophenyl) theophylline, a non-selective adenosine receptor antagonist, at a dose of 30 mg/kg before MA. Animals in the two saline groups received control saline. Fluorescent microspheres (15 µm in diameter, yellow-green fluorescent) were used for MBF measurement in all four groups. ...
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Adenosine is an endogenously released purine nucleoside that signals through four widely expressed G protein-coupled receptors: A1, A2A, A2B, and A3. Of these, A2AR is recognized as mediating major adenosine anti-inflammatory activity. During cutaneous leishmaniasis, adenosine induces immunosuppression, which promotes the establishment of infection. Herein, we demonstrated that A2AR signaling is exploited by Leishmania infantum parasites, the etiologic agent that causes Visceral Leishmaniasis (VL), to successfully colonize the vertebrate host. A2AR gene-deleted mice exhibited a well-developed cellular reaction with a strong Th1-immune response in the parasitized organs. An intense infiltration of activated neutrophils into the disease-target organs was observed in A2AR-/- mice. These cells were characterized by high expression of CXCR2 and CD69 on their cell surfaces and increased cxcl1 expression. Interestingly, this phenotype was mediated by IFN-γ on the basis that a neutralizing antibody specific to
Clinical Application of the Adenosine Triphosphate-based Response Assay in Intravesical Chemotherapy for Superficial Bladder Cancer Adenosine triphosphate;chemotherapy response assay;superficial bladder cancer; Objective: To investigate correlations between adenosine triphosphate chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-based chemotherapy for drug selection in patients receiving intravesical chemotherapy to prevent recurrence of superficial bladder cancer after surgery. Methods: The chemosensitivities of 12 anticancer drugs were evaluated, including 5-Fu ADM, and EPI, using ATP-CRA and primary tumor cell culture in 54 patients. In addition, a further 58 patients were treated according to clinical experience. Differences in post-chemotherapeutical effects between drug sensitivity assay and experience groups were compared. Results: The evaluable rate of the test was 96.3%, the clinical effective rate was 80.8%, the sensitivity rate was 97.6% (41/42), the specificity was
Myocardial perfusion reserve (hyperemic divided by basal myocardial blood flow) describes vasodilator responsiveness of coronaryresistive vessels. The effect of aging and gender on myocardial perfusion reserve remains controversial. Methods: We studied 56 normal volunteers (21 women, 35 men; aged 50 +/- 20 yr, range 21-86 yr) with O-15-water PET to measure myocardial blood flow during basal and hyperemic stales with intravenous dipyridamole (0.56 mg/kg, n = 46) or adenosine (140 mu g/kg/min, n = 10). For comparative analysis, patients were grouped according to age: ,30 yr (n = 11), 30-49 yr (n = 18), 50-69 yr (n = 15) and greater than or equal to 70 yr (n = 12). Results: Overall, basal flow was 1.00 +/- 0.26 ml/min/g and hyperemic flow was 3.31 +/- 1.38 ml/min/g, resulting in a myocardial perfusion reserve of 3.38 +/- 1.35. There was an increase in basal flow with age (r = 0.45, p , 0.025), although hyperemic flow was only lower in patients greater than or equal to 70 yr, causing a significant ...
A-to-I RNA editing is an enzymatic reaction commonly found in the nervous system of various organisms. The mechanism behind this post-transcriptional modification is the hydrolytic deamination of Adenosine to Inosine by a family of enzymes known as Adenosine Deaminases that act on RNA (ADAR). ADARs alter the composition of Adenosine to form Inosine in pre-mRNA. The Inosine is read as a Guanosine by the ribosomes during translation. Alterations may occur due to editing during translation that can result in the production of different amino acids from the original genomically-encoded DNA transcript which can affect the proteins produced. Alterations in the protein products have been shown to lead to various diseases in humans; such as neurodegenerative diseases. A-to-I RNA editing sites have been identified in the para sodium channel gene of Drosophilia melanogaster. We hypothesize that there are potential RNA editing targets in the crustacean Artemia franciscana. Our methods include isolating ...
When given for the evaluation or treatment of a supraventricular tachycardia (SVT), the initial dose is 6 mg, given as a rapid parenteral infusion. Due to adenosines extremely short half-life, the IV line is started as proximal (near) to the heart as possible, such as the cubital fossa. The IV push is often followed with an immediate flush of 10-20 ccs of saline. If this has no effect (i.e., no evidence of transient AV block), a dose of 12 mg can be given 1-2 minutes after the first dose. Some clinicians may prefer to administer a higher dose (typically 18 mg), rather than repeat a dose that apparently had no effect.[dubious - discuss] When given to dilate the arteries, such as in a "stress test", the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol. The recommended dose may be increased in patients on theophylline, since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole ...
Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringers, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringers. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of ...
The formation of new lymphatic vessels, or lymphangiogenesis, is a natural process involved in tissue repair and in the resolution of inflammatory reactions. In some cancers, this process is exploited by the tumor to promote its growth and its metastatic dissemination. Our group recently identified a role for the CD73-adenosine pathway in tumor angiogenesis. As angiogenesis and lymphangiogenesis are similar processes, often occurring in parallel, we suspect that the CD73-adenosine pathway could have a role in the regulation of lymphangiogenesis during inflammatory reactions and in the tumor microenvironment.. To confirm this hypothesis, we used in vivo models of inflammatory lymphangiogenesis induced by the administration of lipopolysaccharide (LPS) or Incomplete Freunds Adjuvant (IFA) in the peritoneal cavity of mice. These two models of peritonitis trigger the formation of new lymphatics in the diaphragm that can be analyzed by flow cytometry. To study tumor lymphangiogenesis, we used a ...
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Both TAR DNA binding protein of 43kDa (TDP-43) pathology and failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2, a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, are the characteristic etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS), the most common adult-onset fatal motor neuron disease. Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes RNA editing at the Q/R site of GluA2, and conditional ADAR2 knockout mice (ADAR2flox/flox/VAChT-Cre.Fast ; AR2 mice) exhibit a progressive ALS phenotype with TDP-43 pathology-like TDP-43 mislocalization in the ADAR2-lacking motor neurons. Because Ca2+-permeable AMPA receptor-mediated mechanism underlies death of motor neurons in the AR2 mice, amelioration of exaggerated Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here we showed that oral perampanel, a selective
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, with the characteristic symptoms of chronic abdominal pain and altered bowel habits (diarrhea, constipation, or both). IBS is a highly prevalent condition, which negatively affects quality of life and is a significant burden on global healthcare costs. Although many pharmacological medicines have been proposed to treat IBS, including those targeting receptors, channels, and chemical mediators related to visceral hypersensitivity, successful pharmacotherapy for the disease has not been established. Visceral hypersensitivity plays an important role in IBS pathogenesis. Immune activation is observed in diarrhea-predominant patients with IBS and contributes to the development of visceral hypersensitivity. Adenosine is a chemical mediator that regulates many physiological processes, including inflammation and nociception. Among its receptors, the adenosine A2B receptor regulates intestinal secretion, motor function, and the ...
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Hereditary deficiency of the enzyme adenosie deaminase (adenosine aminohydrolase, EC 3.5.4.4) results in an immunodeficiency syndrome characterized by a marked reduction in circulating lymphocytes. We have administered 2-deoxycoformycin, a potent inhibitor of adenosine deaminase, to a patient with a lymphoproliferative malignancy. The clinical consequences of pharmacologic inhibition of adenosine deaminase activity included an abrupt decrease in the lymphocyte count, abnormalities of renal and hepatic function, and hemolytic anemia. The plasma concentrations of adenosine and deoxyadenosine rose to peak values of 13 microM and 5 microM, respectively, and erythrocyte dATP levels increased to 110 pmol/10(6) cells over 9 days. There was a corresponding decrease in erythrocyte ATP levels from 128 to , 6 pmol/10(6) cells. A similar profound reductin in ATP occurred in the erythrocytes of a second patient. The rapid and unexpected depletion of ATP associated with dATP accumulation may account, at ...
immune Uncategorized 3-deazaneplanocin A HCl manufacture, Mouse monoclonal to CD106(PE) Background Successful reduction of malaria transmission to very low levels has made Isabel Province, Solomon Islands, a target for early elimination by 2014. qualitative research methods. Results Approximately 33% (8,554/26,221) 3-deazaneplanocin A HCl manufacture of the population of Isabel Province participated in the survey. Only one subject was found to be infected with Plasmodium falciparum (Pf) (96 parasites/L) using Giemsa-stained blood films, giving a prevalence of 0.01%. PCR analysis detected a further 13 cases, giving an estimated malaria prevalence of 0.51%. There was a wide geographical distribution of infected subjects. None reported having travelled outside Isabel Province in the previous three months suggesting low-level indigenous malaria transmission. The qualitative findings provide warning signs that the current community vigilance approach to surveillance will not be sufficient to achieve ...
Nucleoside and nucleobase transporters are important for salvage of purines and pyrimidines and for transport of their analog drugs into cells. However, the pathways for nucleobase translocation in mammalian cells are not well characterized. We identified an Na-independent purine-selective nucleobase/nucleoside transport system in the nucleoside transporter-deficient PK15NTD cells. This transport system has 1,000-fold higher affinity for nucleobases than nucleosides with K m values of 2.5 ± 0.7 μM for [ 3H]adenine, 6.4 ± 0.5 μM for [ 3H]guanine, 1.1 ± 0.1 mM for [ 3H]guanosine, and 4.2 ± 0.5 mM [ 3H]adenosine. The uptake of [ 3H]guanine (0.05 μM) was inhibited by other nucleobases and nucleobase analog drugs (at 0.5-1 mM in the order of potency): 6-mercaptopurine = thioguanine = guanine > adenine ⋙ thymine = fluorouracil = uracil. Cytosine and methylcytosine had no effect. Nucleoside analog drugs with modification at 2′ and/or 5 positions (all at 1 mM) were more potent than adenosine ...
Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed to investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) and pancreatic cancer adenocarcinoma (PDAC). We demonstrate that caffeine and CGS 15943 block proliferation in HCC and PDAC cell lines by inhibiting the PI3K/Akt pathway. Importantly a kinase profiling assay reveals that CGS 15943 targets specifically the catalytic subunit of the class IB PI3K isoform (p110ƴ). These data give mechanistic insight into the action of caffeine and its analogs and they identify these compounds as promising lead compounds to develop drugs that can specifically target this PI3K isoform whose key role in cancer progression is emerging.. ...
by Alberto Garcia-Zamalloa, Jorge Taboada-Gomez. Background Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA =40 U/l (ADA40) and LP=50% (LP50) in three different prevalence scenarios over 11 years in our area.. Materials and Methods Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion ...
TY - JOUR. T1 - Performance of computed tomography-derived fractional flow reserve using reduced-order modelling and static computed tomography stress myocardial perfusion imaging for detection of haemodynamically significant coronary stenosis. AU - Ihdayhid, Abdul Rahman. AU - Sakaguchi, Takuya. AU - Linde, Jesper J.. AU - Sørgaard, Mathias H.. AU - Kofoed, Klaus F.. AU - Fujisawa, Yasuko. AU - Hislop-Jambrich, Jacqui. AU - Nerlekar, Nitesh. AU - Cameron, James D.. AU - Munnur, Ravi K.. AU - Crosset, Marcus. AU - Wong, Dennis T.L.. AU - Seneviratne, Sujith K.. AU - Ko, Brian S.. PY - 2018/11/1. Y1 - 2018/11/1. N2 - Aims: To compare the diagnostic performance of a reduced-order computed tomography-derived fractional flow reserve (CT-FFR) technique derived from luminal deformation and static CT stress myocardial perfusion (CTP).Methods and results: Forty-six patients (84 vessels) with suspected coronary artery disease from a single institution planned for elective coronary angiography ...
Adenosine (Ado) salvage is essential in plant development. The lack of Ado kinase activity (ADK) in Arabidopsis thaliana adk1 adk2 double mutants results in embryonic lethality; reduction of ADK expression causes a pleiotropic phenotype due to the accumulation of Ado inhibiting transmethylation activities. The phenotype of ADK mutants shows that this enzyme plays a critical role in Ado salvage but the functional significance of the other putative Ado recycling enzymes Ado deaminase (ADA) and Ado nucleosidase (ADN) in Arabidopsis thaliana have yet to be elucidated. ADA catalyzes the irreversible deamination of Ado to inosine. The locus At4g04880 (AtADA) of A. thaliana is annotated as encoding a putative ADA, based on its amino acid sequence similarity and the presence of important, conserved catalytic residues. However, indirect and direct spectrophotometric activity assays of the recombinant enzyme demonstrated that the gene product of this locus does not possess ADA activity; complementation ...
Adenosine is an endogenous nucleoside occurring in all cells of the body and is not chemically related to other antiarrhythmic drugs. Adenosine is indicated for the conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). Adenosine is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenosine is not blocked by atropine ...
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Resistant to dipyridamole and dilazep inhibition (anticancer chemotherapeutics drugs).
We found that the modified nucleosides 5,6-dihydrouridine (DHU), Ψ, acp3U, 3-methylcytidine (m3C), 5-methyluridine (m5U), 3-methyluridine (m3U), xanthosine (X), 1-methylguanosine (m1G), m22G, N2,N2,7-trimethylguanosine (m2,2,7G), mcm5s2U, N6-threonylcarbamoyladenosine (t6A) and m6t6A are elevated in the supernatants of MCF-7 cells compared to those of MCF-10A cells. Therefore, we generally considered a compound level as "elevated" when the area ratio exceeds the mean value of the reference cell line by two standard deviation values (2σ-concept) [5]. The methylated nucleoside N6-methyladenosine (m6A) is not included in this list because it can be formed through isomerization of 1-methyladenosine (m1A) and thus could not be normalized.. Especially the levels of m5U with ratios ~4/1 (MCF-7/MCF-10A), m2,2,7G (~2:1), m6t6A (~2:1) and acp3U (~2:1) should be pointed out.. m5U is present in eukaryotic tRNA and rRNA [22]. Roe and Tsen postulated, that this nucleoside might be involved in the regulation ...
The 105,000 x g supernatant fluid (S[subscript HS]) from extracts of pea seedlings (Pisum sativum, var. Alaska) etiolated for 60 hours yielded a very potent adenosine triphosphatase activity. This activity was designated as an apyrase when the reaction stoichiometry indicated that adenosine triphosphate (ATP) was hydrolyzed to adenosine monophosphate (AMP) and two moles of inorganic phosphate (P[subscript i]). The apyrase has been purified 88-fold with 40% recovery from acetone powders of the S[subscript HS]. This 6-day procedure involved filtration of the acetone powder solutions through Sephadex G-200 and G-75 followed by protamine sulfate treatment to remove polyanionic material. After film dialysis the enzyme activity was chromatographed on carboxymethyl cellulose (CMC) with a gradient NaCl elution. A second more rapid purification scheme was used to purify extracts of acetone powders to 79- to 100-fold with overall yield of 67% to ,100%. This 15-hour scheme involved protamine treatment of ...
Treatments with Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with mutated BRCA1 or BRCA2 genes a new and in many cases effective option for disease control. There is potentially a large patient population that may also benefit from PARP inhibitor treatment, either in monotherapy or in combination with chemotherapy. Here, we describe the multifaceted role of PARP inhibitors and discuss which treatment options could potentially be useful to gain disease control without potentiating side effects.
20762-30-5 - PWJFNRJRHXWEPT-AOOZFPJJSA-N - Adenosine diphosphate ribose - Similar structures search, synonyms, formulas, resource links, and other chemical information.
Zinc adenosine triphosphate - Surfactant - SAAPedia - SAAPedia(Surfactant.TOP),Surfactant,Anionic surfactants, Cationic surfactants, Non-ionic surfactants, Zwitterionic surfactants, Polymer Surfactants, Fluoro surfactants, Silicone surfactants, Biosurfactants, Natural surfactants, Special surfactants - Page1
The nucleoside transport inhibitor dipyridamole can increase the cytotoxicity of 5-fluorouracil in a human colon cancer cell line (HCT 116) without affecting the total amount of fluorouracil incorporated into the acid soluble and insoluble fractions (J. L. Grem and P. H. Fischer, Cancer Res., 45: 2967-2972, 1985). We now report that dipyridamole altered the pattern of fluorouracil metabolism and provided a selective increase in intracellular fluorodeoxyuridine monophosphate (FdUMP) levels. At 2 and 4 h after exposure to fluorouracil and dipyridamole, FdUMP levels were approximately 5-fold higher in the presence of dipyridamole. The ratio of FdUMP to fluorouridine triphosphate at 4 h was substantially increased in the presence of dipyridamole (0.4 ± 0.05) compared to fluorouracil alone (0.08 ± 0.03). In cells preloaded with fluorodeoxyuridine (FdUrd), dipyridamole potently inhibited the efflux of FdUrd, leading to an increased retention of intracellular FdUMP. One h following removal of ...
[05-06-2011] The U.S. Food and Drug Administration (FDA) is alerting the healthcare community about syringe connection problems when certain needleless glass syringes containing the cardiac drugs adenosine and amiodarone are used with particular types of intravenous (IV) access systems.
Adenosine analogues which act selectively at adenosine receptors and which act in general as adenosine antagonists are disclosed. From in vitro studies it is known that specific physiological effects can be distinguished as a result of this selectivity and that adenosine receptor activity in vitro correlates with adenosine receptor activity in vivo. Pharmaceutical preparations of the subject compounds can be prepared on the basis of the selective binding activity of the compounds disclosed herein which will enhance certain physiological effects while minimizing others, such as decreasing blood pressure without decreasing heart rate.
Adenosine is an important mediator of the endogenous defense against ischemia-induced injury in the heart. Adenosine can achieve cardioprotection by mediating the effect of ischemic preconditioning and by protecting against myocyte injury when it is present during the infarct-producing ischemia. A novel adenosine A3 receptor can mediate this protective function. 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. 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. Prolonged hypoxia with glucose deprivation, causing myocyte injury and adenosine release, was used to simulate ischemia in cultured chick embryo ventricular myocytes. During simulated
Adenosine is a multi-functional physiological molecule found abundantly in the body. It is one of the important components of ATP cellular energy metabolism. Adenosine has diverse actions as a ligand on many different types of cells and tissues acting via specific receptors. Currently, four subtypes of adenosine receptors are described, namely, the A1, A2A, A2B and A3 receptors. Neuroblastoma, mostly found in young children, is a malignant tumor derived from peripheral neurons in the body. Several different types of neuroblastoma cell lines of human origin have been established and contributed to the studies of neuroblastoma itself, neuronal differentiation, neurotransmitters, alcoholism, Alzheimers disease and other neuronal diseases and disorders. In 1987, it was shown by Abbracchio et al. that a human neuroblastoma cell line, IMR32, could be induced to differentiate into cells that have a more neuronal morphology, with long neurites, by an adenosine receptor agonist ...
The review summarizes data evaluating the role of adenosine receptor signaling in murine hematopoietic functions. The studies carried out utilized either non-selective activation of adenosine receptors induced by elevation of extracellular adenosine or by administration of synthetic adenosine analogs having various proportions of selectivity for a particular receptor. Numerous studies have described stimulatory effects of non-selective activation of adenosine receptors, manifested as enhancement of proliferation of cells at various levels of the hematopoietic hierarchy. Subsequent experimental approaches, considering the hematopoiesis-modulating action of adenosine receptor agonists with a high level of selectivity to individual adenosine receptor subtypes, have revealed differential effects of various adenosine analogs. Whereas selective activation of A(1) receptors has resulted in suppression of proliferation of hematopoietic progenitor and precursor cells, that of A(3) receptors has led to ...
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Disclosed are processes for the synthesis of novel compounds that are A.sub.2B adenosine receptor antagonists, having the structure of Formula I or Formula II: ##STR00001## by cyclizing a compound of the formula (3): ##STR00002##
... -First A2A Adenosine Receptor Agonist Approved for Use as Pharmacolo... Stress Agent in Myocardial Perfusion Imaging- ...PALO ALTO Calif. and DEERFIELD Ill. April 10 FirstCall/...Lexiscan is the first A2A adenosine receptor agonist shown to be safe...,CV,Therapeutics,and,Astellas,Announce,FDA,Approval,for,Lexiscan(TM),(regadenoson),Injection,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
BACKGROUND: Haemodialysis (HD) sometimes accelerates left ventricular failure (LVF). As adenosine (ADO) is strongly implicated in cardiovascular functions, particularly via A(2A) receptor activation and as changes of peripheral A(2A) receptors mirror
Adenosine mediates many physiological functions via activation of extracellular receptors. The modulation of cell growth by adenosine was found to be receptor-mediated. In A431 cells adenosine evoked a biphasic response in which a low concentration (~10 μM) produced inhibition of colony formation but at higher concentrations (up to 100 μM) this inhibition was progressively reversed. Evidence for the involvement of A1 (inhibitory) and A2 (stimulatory) adenosine receptors in regulating cell growth of these tumor cells was obtained through plating efficiency studies based on the relative potency of adenosine agonists and antagonists. When both A1 and A2 receptors were blocked, colony formation or growth was not inhibited at low concentrations of adenosine but was inhibited at high adenosine concentrations ...
Particularly preferably, Z21 is 2,4-dichloro-1,3,5-triazin-6-ylf 2-chloro-4-(3-(2-suifatoethylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-chloro-4-(4-(2-su!fatoethy!sulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-chloro-4-(3-(vinylsulfonyl)-phenylarnino)-1 t3,5-triazin-6-yl, 2-chloro4-(4-(vinylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-ch!oro-4-(N-methy!-N-(2-(2-sulfatoethylsulfonyl)-ethy!)-amino)-1,3,5-triazin-6-yl, 2-ch!oro-4-(N-phenyl-N-(2-(2-sulfatoethylsulfonyl)-ethyl)-amino)-1,3,5-tria2in-6-yl, 2-fluoro-4-morpholino-1,3,5-triazin-6-yI, 2-fluoro-4-(2-sulfophenyl-amino)-1,3,5-triazin-6-yl, 2-fluoro-4-(3-sulfophenylamino)-1,3,5-triazin-6-yl, 2-fluoro-4-(4-sulfophenylamino)-1,3,5-triazin-6-yl, 2-fiuoro-4-(3-trimethylammonio-phenylamino)-1,3,5-triazin-6-ylf 2-fIuoro-4-(4-trirnethylammoniophenylamino)-1,3,5-triazin-6-yl, 2-fluoro-4-(3-(2-sulfatoethylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl( 2-fluoro-4-(4-(2-sulfatoethylsulfonyl,-phenylamino)-1 f3,5-triazin-6-yl, ...
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
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Restenosis, characterized by enhanced neointimal lesion development attributable to excessive SMC proliferation, is still a major concern after percutaneous transluminal coronary angioplasty treatment of patients experiencing (acute) cardiovascular syndromes. In search for novel therapeutic treatment modalities, our attention was turned to the A2B adenosine receptor, which has been shown to be involved in the proliferation of vascular SMCs in rats, as well as in humans.14,27,28 In this study, we thus sought to investigate the therapeutic potential of BAY60-6583, an agonist for this receptor subtype. The compound behaved as a selective probe for the (human) adenosine A2B receptor in radioligand-binding studies, although it displayed affinity for the adenosine A1 receptor. In fact, this is the first report that shows a full radioligand-binding analysis over all 4 subtypes of human adenosine receptors. Auchampach et al29 evaluated the compound in radioligand-binding studies on adenosine A2B ...
We have demonstrated previously that both acute and chronic oral administration of adenosine have novel functions such as anti-hypertensive effects and improved hyperlipidaemia in stroke-prone spontaneously hypertensive rats (SHRSP) fed a normal diet. The purpose of the present study was to investigate the effect of adenosine administration on metabolic syndrome-related parameters in SHRSP fed a high-fat diet. Six-week-old rats were divided into three groups, and were administered either water (control) or adenosine (10 or 100 mg/l) for 8 weeks. During this period, the rats had free access to a high-fat diet based on AIN-93M. The results showed that hypertension, plasma lipid, NO, insulin, glucose and urinary 8-hydroxy-2-deoxyguanosine levels improved significantly in both adenosine groups. The mRNA expression levels of genes involved in anti-oxidative activity and adenosine receptors were also altered in the adenosine groups. Administration of adenosine also increased plasma adiponectin ...
Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A1-R, A2A-R and A3-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A2A-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A2A-R in FVB mice. Echocardiograms were obtained at baseline, 2, 4, 8, 12, 14 weeks and hearts were harvested at 14 weeks, when WT mice developed a significant decrease in cardiac function, an increase in end systolic and diastolic dimensions, a higher heart weight to body weight ratio (HW/BW), and marked fibrosis when compared
Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types - A1, A2A, A2B, and A 3Rs - regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory-vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The roles of the ARs in beneficial modulation of cardiac and vascular function, growth and stress-resistance render them attractive therapeutic targets. However, interactions between ARs and with other receptors, and their ubiquitous
In the central nervous system, the nucleoside adenosine regulates neuronal activity by modulating the actions of other neurotransmitter systems, thereby influencing many different physiological processes and behaviors. Adenosinergic mechanisms are especially important in fine-tuning glutamatergic neurotransmission. Astrocytic release of adenosine triphosphate and its subsequent extracellular breakdown provides adenosine to drive homeostatic sleep. Acute ethanol (alcohol) exposure increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol exposure leads to downregulated adenosine signaling that underlies insomnia, a major predictor of relapse. Adenosine gates glutamatergic input to the circadian clock located in the suprachiasmatic nucleus of the hypothalamus, modulating both photic (light-induced) and nonphotic (behaviorally-induced) synchronization of circadian activity rhythms. A recent study using mice lacking the equilibrative ...
P>Adenosine is a well-described anti-inflammatory modulator of immune responses within peripheral tissues. Extracellular adenosine accumulates in inflamed and damaged tissues and inhibits the effector functions of various immune cell populations, including CD8 T cells. However, it remains unclear whether extracellular adenosine also regulates the initial activation of naive CD8 T cells by professional and semi-professional antigen-presenting cells, which determines their differentiation into effector or tolerant CD8 T cells, respectively. We show that adenosine inhibited the initial activation of murine naive CD8 T cells after alpha CD3/CD28-mediated stimulation. Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of naive CD8 T cells. Remarkably, adenosine interfered efficiently with CD8 T-cell priming by professional antigen-presenting cells (dendritic cells) and semi-professional antigen-presenting cells ...
Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = ...
Caffeine, an adenosine receptor antagonist, blocks various receptors in the brain which are activated by adenosine. Initial results of the team of researchers had already indicated that the blockade of the adenosine receptor subtype A2A in particular could play an important role. Initially, Prof. Müller and her colleagues developed an A2A antagonist in ultrapure and water-soluble form (designated MSX-3). This compound had fewer adverse effects than caffeine since it only blocks only the A2A adenosine receptor subtype, and at the same time it is significantly more effective. Over several weeks, the researchers then treated genetically altered mice with the A2A antagonist. The mice had an altered tau protein which, without therapy, leads to the early development of Alzheimers symptoms ...
A series of 5-carbamoyl and 5-thionocarbamoyl derivatives of 2-C-methyl analogues of the A(1) adenosine receptor (A(1)AR) full agonists N(6)-cyclopentyladenosine (CPA), 2-chloro-N(6)-cyclopentyladenosine (CCPA), N(6)-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N(6)-cyclopentylamino series, the 5-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N(6)-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine A(1)AR. The 5-methylthionocarbamoyl derivative of 2-Me-CCPA showed the best affinity at porcine A(1)AR with a K(i) value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at A(1)AR and very ...
The properties of adenosine attenuation of catecholamine-elicited increases in peak contractile force, rate of force development, and rate of relaxation were studied in isolated rat atria. Adenosine, at a concentration that did not cause a direct depressant effect by itself, was capable of reducing by approximately 15% the increase in the contractile parameters elicited by isoproterenol. This reduction was not overcome by elevating the catecholamine concentration. The adenosine reduction was prevented by theophylline or the presence of adenosine deaminase. The reduction appears to be independent of the acetylcholine-mediated reduction of catecholamine responses. Adenosine reduced the positive inotropic responses elicited by norepinephrine and epinephrine but not phenylephrine. Adenosine deaminase in oxygenated atria potentiated the catecholamine-elicited contractile responses and reduced the progressive fall of the elevated contractile responses observed with continual catecholamine stimulation. In
In the current study, the combination of T62 and clonidine produced a synergistic interaction in rats with incisional pain. Synergy usually indicates that the two drugs have different final pathways to produce their effect, although other levels of interaction, such as altered drug disposition, can also be responsible. We did not measure tissue concentrations of drugs, so we cannot exclude a pharmacokinetic mechanism of synergy in the current study. Nonetheless, the observation of synergy is somewhat surprising if, as indicated by studies with spinal nerve ligation, the effect of T62 relies entirely on stimulating spinal norepinephrine release, which acts on α2adrenoceptors. One would in that case expect an additive interaction, and intrathecal adenosine and clonidine do interact additively in spinal-ligated rats. 14 In contrast, a synthetic adenosine agonist interacts synergistically with clonidine in acute thermal nociception tests in normal rats. 20 In addition, idazoxan only partially ...
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Adenosine has long been thought to play a role in the pathogenesis of allergic airway disease and asthma (9, 13, 30, 45). However, the mechanisms of adenosine-mediated lung damage are poorly understood. In the current study, we used cDNA microarray technology to profile the expression of 1,176 known regulatory genes in trying to uncover some of the regulatory pathways involved in adenosine-mediated lung damage. Our laboratory (3, 6) has used a mouse model in which lung adenosine levels are markedly elevated in association with lung inflammation and damage. The results of this study identify a number of differentially expressed genes that may be regulated by adenosine and hence play a pivotal role in modulating the underlying lung pathology.. ADA enzyme therapy, which is directed at lowering adenosine levels, effectively altered differential gene expression in ADA-deficient lungs in association with attenuating lung eosinophilia. This suggests that the differential gene expression observed in ...
The initial studies to test the hypothesis that adenosine release mediates the anti-inflammatory effects of methotrexate were performed in vitro. In these studies, methotrexate treatment increased adenosine release from cultured endothelial cells and fibroblasts and the adenosine released diminished stimulated neutrophil adhesion to the monolayers of cultured cells (Cronstein et al., 1991). Subsequent in vivo studies confirmed the hypothesis that adenosine mediates the anti-inflammatory effects of methotrexate; pharmacologically relevant doses of methotrexate induce intracellular AICAR accumulation in splenocytes, increase adenosine concentrations in inflammatory exudates, and diminish leukocyte accumulation at an inflamed site (Cronstein et al., 1993). Moreover, the increase in exudate adenosine concentration was responsible for the anti-inflammatory effects of the drug since adenosine receptor antagonists or adenosine deaminase, an enzyme which converts adenosine to the receptor-inactive ...
Abstract BACKGROUND: In view of the multiple effects of adenosine on kidney function, this study aimed to determine the expression of adenosine receptors (AR) along the rat and mou..
Adenosine is a modulator of many physiological and pathophysiological processes in the central nervous system (CNS). Blockade of the adenosine receptors A1ARs and A2AARs has shown beneficial neuroprotective effects in animal models and in clinical studies of Parkinsonss disease (PD) and Alzheimers disease (AD). Furthermore, selective inhibitors of the monoamine oxidase A (MAO-A) are applied as adjunctive therapeutics for PD, as they protect the brains of PD patients from oxidative stress. Nevertheless, there is still no satisfactory multitarget drug approach which inhibits MAO-A and the two adenosine receptors A1ARs and A2AARs. This invention provides newly designed tricyclic xanthine derivatives which allow overcoming this problem. A variety of 69 derivatives were prepared and evaluated in radioligand binding studies at adenosine receptors and for their ability to inhibit monoamine oxidases. Potent dual-target-directed A1/A2A adenosine receptor antagonists were identified. Several compounds ...
The main storage organ in insects is the fat body, a counterpart of mammalian liver and adipose tissue. The deposition of stores as well as the stimulation of their release is intensively studied in many insect models, which show that the basic regulation of carbohydrate metabolism is similar to that in higher organisms (Hudson et al., 1993). As shown in Fig. 6, glycogen synthesis and breakdown is regulated by glycogen synthase and glycogen phosphorylase. The energy-demanding processes in insects stimulate the release of energy from the fat body stores through the action of AKHs (reviewed in Gäde and Auerswald, 2003). AKH, a counterpart of mammalian glucagon, binds to G-protein-coupled receptors and, in the case of carbohydrate metabolism, activates glycogen phosphorylase via cAMP production and Ca2+ (binding to Gs and Gq subunits). This includes regulation by Ca2+-dependent PhK.. Extracellular adenosine can affect carbohydrate metabolism in the fat body by two possible mechanisms (Fig. 6): ...
Read A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics by with Rakuten Kobo. This book, with its 16 chapters, documents the present state of knowledge of the adenosine A receptor. It covers a wide ...
4,6-Dimethyl-1,3,5-triazin-2-amine hydrate, ≥95%, Maybridge Amber Glass Bottle; 10g 4,6-Dimethyl-1,3,5-triazin-2-amine hydrate, ≥95%, Maybridge Dimethylthie to...
New research undertaken at Saint Louis University, in concert with researchers from the National Institutes of Health, the University of Arizona, and 2 institutes in Quebec, reports the discovery of drugs targeting the A3 adenosine receptor (A3AR) that can "turn off" pain signals in the spinal cord to provide relief from chronic pain. The findings were published in the April issue of the Journal of Neuroscience. The study supports earlier demonstrations that 2 drugs that target the A3AR-IB-MECA and MRS5698-were effective in treating several models of chronic pain, including painful chemotherapy-induced neuropathy, metastatic cancer pain, and nerve injury.. In this study, researchers confirmed that A3AR drugs not only relieved pain, but did so by activating an inhibitory transmitter system known as the gamma amino-butyric acid (GABA) system. In areas of the spinal cord and brain dedicated to pain processing, A3AR activation promoted GABA signaling by preventing the breakdown and removal of GABA ...
Symptoms of Adenosine triphosphatase deficiency, anaemia due to including 12 medical symptoms and signs of Adenosine triphosphatase deficiency, anaemia due to, alternative diagnoses, misdiagnosis, and correct diagnosis for Adenosine triphosphatase deficiency, anaemia due to signs or Adenosine triphosphatase deficiency, anaemia due to symptoms.
Abstract: In presence of adenosine (10(-7)-10(-6) M) content of nuclear 3H-hydrocortisone-receptor complexes was increased in rat thymus lymphocytes, while amount of these complexes was decreased in cytosol of these cells. DEAE-cellulose chromatography of the 3H-hydrocortisone-receptor complexes demonstrated that adenosine 1.10(-6) M altered the ratio between active and non-active forms of the hormone-receptor complex. Adenosine appears to regulate transformation and translocation of the glucocorticoid-receptor complexes into the cell-target nuclei cAMP-dependent apparatus ...
Adenosine deaminase has been shown to consist of three molecular weight forms, A, B, and C. In higher mammals, the A and C forms are dominant while in lower mammals, the B and C forms are dominant. In this work, the B and C forms were isolated from the frog liver and several kinetic parameters were determined.Ammonium sulfate salt fractionation, starting at 40 percent and increased by 5 percent increments to 80 percent was used to separate the two forms. The B form adenosine deaminase was predominantly found in the 50 to 60 percent precipitate fractions while the C form was predominant in precipitate fractions containing more than 60 percent ammonium sulfate. The rechromatographed B and C forms were subjected to isoelectric focusing and thin layer electrophoresis. The B form separated into three activity bands while the C form separated into two activity bands`. Michaelis constant values were determined to be 4.61 X 10-5M and 2.00 X 10-5M for the B and C forms with adenosine as a substrate, ...
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.
3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile chemical properties, What are the chemical properties of 3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile 86375-28-2, What are the physical properties of 3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile ect.
Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor | Garvan Institute of Medical...  Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor | Garvan Institute of Medical...
... the endogenous adenosine by increasing the number of adenosine receptors instead of administering an adenosine receptor agonist ... the endogenous adenosine by increasing the number of adenosine receptors instead of administering an adenosine receptor agonist ... A novel adenosine A3 receptor can mediate this protective function. One approach to achieve cardioprotection is to enhance ... A novel adenosine A3 receptor can mediate this protective function. One approach to achieve cardioprotection is to enhance ...
more infohttps://www.garvan.org.au/research/publications/1164
Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors. | IRIS Uniroma1  Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors. | IRIS Uniroma1
Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer ... The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA) run-down but only in approximately 20% ... Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer ... receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) ...
more infohttps://iris.uniroma1.it/handle/11573/224547
Medicinal chemistry and pharmacology of A2B adenosine receptors | Pubblicazioni Scientifiche Unicam  Medicinal chemistry and pharmacology of A2B adenosine receptors | Pubblicazioni Scientifiche Unicam
Hence, A2B adenosine receptor agonists could be useful in the treatment of cardiac diseases like hypertension or myocardial ... A3/A2B = 360). Among non-xanthine derivs. very promising are substituted purines, in which combination of appropriate ... The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven ... The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven ...
more infohttps://pubblicazioni.unicam.it/handle/11581/242340
A.sub.2B adenosine receptor antagonists - Patent # 7125993 - PatentGenius  A.sub.2B adenosine receptor antagonists - Patent # 7125993 - PatentGenius
A.sub.2B adenosine receptor antagonists, having the structure of Formula I or Formula II: ##STR00001## by cyclizing a compound ... A.sub.2A and A.sub.2B adenosine receptors are coupled to Gs proteins and thus agonists for A.sub.2A adenosine receptor (such as ... 1 mM EDTA and 10 mM MgCl.sub.2 for CHO-A3) supplemented with 1 Unit/mL adenosine deaminase. The assays were incubated for ... A.sub.1 and A.sub.3 adenosine receptors are coupled to Gi proteins and thus agonists for A.sub.1 adenosine receptor (such as ...
more infohttp://www.patentgenius.com/patent/7125993.html
Adenosine A3 receptor agonist inhibits retinal ganglion cell apoptosis in vivo | IOVS | ARVO Journals  Adenosine A3 receptor agonist inhibits retinal ganglion cell apoptosis in vivo | IOVS | ARVO Journals
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 ...
more infohttps://iovs.arvojournals.org/article.aspx?articleid=2149180
Molecules | Free Full-Text | Structural Probing and Molecular Modeling of the A3 Adenosine Receptor: A Focus on Agonist Binding  Molecules | Free Full-Text | Structural Probing and Molecular Modeling of the A3 Adenosine Receptor: A Focus on Agonist Binding
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, ...
more infohttp://www.mdpi.com/1420-3049/22/3/449
Federal Register
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      Prospective Grant of Start-Up Exclusive Evaluation Option License Agreement: A3 Adenosine...  Federal Register :: Prospective Grant of Start-Up Exclusive Evaluation Option License Agreement: A3 Adenosine...
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 ...
more infohttps://www.federalregister.gov/documents/2014/12/09/2014-28749/prospective-grant-of-start-up-exclusive-evaluation-option-license-agreement-a3-adenosine-receptor
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 ... 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 ...
more infohttps://www.spandidos-publications.com/ijo/33/2/287/abstract
Advances in drug discovery: Can-Fite moves towards opening Phase 3 study of adenosine A3 receptor agonist, CF101 in rheumatoid...  Advances in drug discovery: Can-Fite moves towards opening Phase 3 study of adenosine A3 receptor agonist, CF101 in rheumatoid...
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. ...
more infohttp://leaddiscovery.blogspot.co.uk/2015/01/can-fite-moves-towards-opening-phase-3.html
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...
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) ...
more infohttps://www.niddk.nih.gov/research-funding/technology-advancement-transfer/research-materials-licensing/methanocarba-adenosine-derivatives
Adenosine A₃ Receptor Agonist, 2-Cl-IB-MECA - CAS 163042-96-4 - Calbiochem CAS 163042-96-4 | 119139  Adenosine A₃ Receptor Agonist, 2-Cl-IB-MECA - CAS 163042-96-4 - Calbiochem CAS 163042-96-4 | 119139
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 ...
more infohttp://www.merckmillipore.com/ZA/en/product/Adenosine-A3-Receptor-Agonist-2-Cl-IB-MECA-CAS-163042-96-4-Calbiochem,EMD_BIO-119139
More Biologic Therapies Expected To Treat Advanced Plaque Psoriasis | P&T Community  More Biologic Therapies Expected To Treat Advanced Plaque Psoriasis | P&T Community
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 ...
more infohttps://www.ptcommunity.com/journal/article/full/2016/6/388/more-biologic-therapies-expected-treat-advanced-plaque-psoriasis
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in...  Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in...
Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ... Effects of adenosine receptor agonists of the A1, A2A and A3 subtypes on the proinflammatory activity of human neutrophils in ...
more infohttps://repository.up.ac.za/handle/2263/29077
A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion | Springer for...  A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion | Springer for...
Introduction Although activation of A3adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the ... N6-disubstituted adenine nucleosides as highly potent and selective A3 adenosine receptor agonists. J Med Chem 2005, 48: 1745- ... we compared the effect of the A3 adenosine agonist IB-MECA with the newly synthesized, highly selective A3 adenosine receptor ... Molecular cloning and characterization of an adenosine receptor: the A3adenosine receptor. Proc Natl Acad Sci USA 1992, 89: ...
more infohttps://rd.springer.com/article/10.1186/cc4893
Adenosine A3 receptor - Wikipedia  Adenosine A3 receptor - Wikipedia
... 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". ...
more infohttps://en.wikipedia.org/wiki/Adenosine_A3_receptor
Global Ophthalmic Drugs Market Forecast 2019-2029 - Visiongain  Global Ophthalmic Drugs Market Forecast 2019-2029 - Visiongain
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) - ...
more infohttps://www.visiongain.com/report/global-ophthalmic-drugs-market-forecast-2019-2029/
Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of serum G-CSF and might be usable as an auxiliary means in G...  Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of serum G-CSF and might be usable as an auxiliary means in G...
... pharmacological therapy of the acute radiation disease using a cyclooxygenase-2 inhibitor and an adenosine A3 receptor agonist ... Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A₃ receptor agonist on hematopoiesis in sublethally ... Activation of adenosine A(3) receptors potentiates stimulatory effects of IL-3, SCF, and GM-CSF on mouse granulocyte-macrophage ... Synergistic effect of granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on neutrophil ...
more infohttps://www.semanticscholar.org/paper/Meloxicam%2C-an-inhibitor-of-cyclooxygenase-2%2C-the-of-Hofer-Posp%C3%AD%C5%A1il/d5d1accab340618172eeda44371979d48db710db
Garden of therapeutic delights: new targets in rheumatic diseases | Arthritis Research & Therapy | Full Text  Garden of therapeutic delights: new targets in rheumatic diseases | Arthritis Research & Therapy | Full Text
Targeting tyrosine kinases downstream of growth factor receptors might also reduce fibrosis in conditions like systemic ... In addition to plasma membrane G protein-coupled chemokine receptors, small molecules can be designed to block intracellular ... adenosine A3 receptors), proteases (for example, collagenases), ion channels (for example, P2X7 receptor), and innate immune ... Adenosine A3 receptor agonist. IB-MECA (CF101). Phase II in RA.. Ion channels ...
more infohttps://arthritis-research.biomedcentral.com/articles/10.1186/ar2556
世界の点眼薬市場予測 2018-2028年 / Visiongain  世界の点眼薬市場予測 2018-2028年 / Visiongain
10.8.1 CF101 (adenosine A3 receptor agonist) - Can-FiteBioPharma 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) - ...
more infohttp://www.dri.co.jp/auto/report/visiongain/vgpha0054.html
Patents filed at May 08 2018 | Methods of using compositions comprising variants and fusions of FGF19
     polypeptides for...  Patents filed at May 08 2018 | Methods of using compositions comprising variants and fusions of FGF19 polypeptides for...
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 ...
more infohttp://www.patents.com/isd-20180508-p81.html
  • Adenosine can achieve cardioprotection by mediating the effect of ischemic preconditioning and by protecting against myocyte injury when it is present during the infarct-producing ischemia. (garvan.org.au)
  • Hence, (S)-2-phenylhydroxypropynylNECA (PHPNECA), with an EC50 = 0.22 μM, proved to be the most potent A2B agonist reported so far. (unicam.it)
  • Adenosine is an important mediator of the endogenous defense against ischemia-induced injury in the heart. (garvan.org.au)
  • The objective of the present study was to investigate whether genetic manipulation of the cardiac myocyte, achieved by gene transfer and overexpression of the human A3 receptor cDNA, renders the myocytes resistant to the deleterious effect of ischemia. (garvan.org.au)
  • Prolonged hypoxia with glucose deprivation, causing myocyte injury and adenosine release, was used to simulate ischemia in cultured chick embryo ventricular myocytes. (garvan.org.au)
  • 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)
  • Also, increased expression of the A3 receptor caused an enhanced cardioprotective effect by the preconditioning ischemia. (garvan.org.au)
  • Overexpressing the adenosine A1 receptor also led to increased protection against ischemia-induced myocyte injury as well as an enhanced preconditioning effect. (garvan.org.au)
  • Through A2B receptors adenosine seems to cause mast cells degranulation, vasodilation, cardiac fibroblast proliferation, inhibition of Tumor Necrosis Factor (TNF-α), increased synthesis of interleukin-6 (IL-6), stimulation of Cl- secretion in intestinal epithelia and hepatic glucose prodn. (unicam.it)
  • 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)
  • The A2B receptors show a ubiquitous distribution, the highest levels are present in cecum, colon and bladder, followed by blood vessels, lung, eye and mast cells. (unicam.it)
  • the 3-unsubstituted 1-alkyl analogs resulted more A2B selective with the 8-[4-[(N-(2-hydroxyethyl)carboxamidomethyl)oxy]phenyl]-1-propylxanthine (60) showing the highest affinity (Ki = 1.2 nM) and selectivity (A1/A2B = 60, A2A/A2B = 1,790, A3/A2B = 360). (unicam.it)
  • I(GABA) run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is tonically influenced by A2A but not by A1 receptors. (uniroma1.it)
  • Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer therapeutic opportunities. (uniroma1.it)
  • The monosubstitution on N6-position of adenosine is well tolerated and that position appears to be a useful site for increasing A2B potency. (unicam.it)
  • Among substituents in 2-position of adenosine only 1-alkynyl chains are effective for A2B potency. (unicam.it)
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