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.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.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.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.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).Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.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.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.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: 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.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.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 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.Aminophylline: A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.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.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.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)Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.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.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.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.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)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.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.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.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.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 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.Adenine NucleotidesPurinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.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.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.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.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.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)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).GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).Piperidines: A family of hexahydropyridines.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.GABA-A Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.Kinetics: The rate dynamics in chemical or physical systems.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.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.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Receptors, 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.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.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.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.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.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.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.Serotonin 5-HT4 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.TriazolesSignal 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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.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.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.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.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.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.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.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.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)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.Benzazepines: Compounds with BENZENE fused to AZEPINES.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.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, 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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Mice, Inbred C57BLColforsin: 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.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.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.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).Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.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)PyrrolidinesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.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.Sulfonamides: A group of compounds that contain the structure SO2NH2.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.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.Deoxyadenosines: Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Piperazines2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine: A selective D1 dopamine receptor agonist used primarily as a research tool.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)Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.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)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.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.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.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.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.Nucleoside Transport Proteins: Proteins involved in the transport of NUCLEOSIDES across cellular membranes.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.Quinpirole: A dopamine D2/D3 receptor agonist.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Behavior, Animal: The observable response an animal makes to any situation.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.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.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.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.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.Apyrase: A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 3.6.1.5.Extracellular Space: Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Cannabinoids: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.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.Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.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.Coronary Circulation: The circulation of blood through the CORONARY VESSELS of the HEART.Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 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.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.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.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESHypoxanthines: Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.Heart: The hollow, muscular organ that maintains the circulation of the blood.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.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.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.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.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.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.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.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.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.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.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.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.Purinergic Agonists: Compounds that bind to and activate PURINERGIC RECEPTORS.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.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.NorbornanesPurinergic P2Y Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.QuinoxalinesDrug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... the pharmacological blockade of A1 may have clinical utility. Theophylline and caffeine are nonselective adenosine antagonists ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ...
... 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 ... The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or ... Like other methylated xanthine derivatives, theophylline is both a competitive nonselective phosphodiesterase inhibitor, which ...
... which is a competitive antagonist of this protein. As with the A1, the A2A receptors are believed to play a role in regulating ... adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels". ... Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ...
Ramatroban, vidupiprant, and Bay U3405 are non-selective (i.e. known to influence other receptors) antagonists of DP2.[9] ... thromboxane A2. The cyclopentenone prostaglandins, PGJ2, Δ12-PGJ2, and 15-d-Δ12,14-PGJ2 are spontaneously formed or protein- ... is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and ... prostaglandin D receptor activity. • G-protein coupled receptor activity. • prostaglandin J receptor activity. • prostaglandin ...
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... the pharmacological blockade of A1 may have clinical utility. Theophylline and caffeine are nonselective adenosine antagonists ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ...
... hypothesis that intracerebroventricular CNS administration of the selective adenosine A1 and A2 receptor agonist NECA ... NECA was chosen for the study because caffeine is a nonselective adenosine receptor antagonist, and it is not known which of ... Protein linked to cancer acts as a viscous glue in cell division 07.07.2020 , Rensselaer Polytechnic Institute ... study to determine the effects of intracerebroventricular injection of caffeine and the adenosine A1 and A2 receptor agonist 5 ...
... designated A1, A2A, A2B and A3 are currently known. In this study all human subtypes were stably transfected into Chinese ... Four adenosine receptor subtypes of the family of G protein-coupled receptors, ... as the most potent antagonist at this receptor subtype. The A3 receptor was characterized utilizing the nonselective agonist [ ... Four adenosine receptor subtypes of the family of G protein-coupled receptors, designated A1, A2A, A2B and A3 are currently ...
... 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 ... The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or ... Like other methylated xanthine derivatives, theophylline is both a competitive nonselective phosphodiesterase inhibitor, which ...
which receptors are paired with which G proteins HAVE 1 M and M --- Gq. - H2, a1, V1, M1 and M3. MAD 2s ----- Gi. - M2, a2, D2 ... a2 agonist for hypertensive urgency, ADHD, severe pain. - tox: CNS depression, bradycardia, hypotension, respiratory depression ... muscarinic antagonist that acts on GI and resp. - parenteral: preop use to reduce airway secretions. - oral: drooling, peptic ... reversible nonselective alpha blocker. - give to pts on MAOis who eat foods with tyramine ...
... forms nonselective membrane channels, structurally similar to gap junction hemichannels, that is permeable to ions, nucleotides ... forms nonselective membrane channels, structurally similar to gap junction hemichannels, that is permeable to ions, nucleotides ... Functional modulators include NMDA, A1/A2 adenosine receptors, Kvβ 3 potassium channels and fibroblast growth factor-1 (FGF-1 ... and TRPV4 receptors; (ii) interactions with Ca2+-mobilizing G protein-coupled receptors, such as P2Y and PAR1 receptors that ...
Methoxamine and phenylephrine are synthetic a1-receptor has b1-receptor antagonist and b2-receptor agonist prop- agonists, used ... a2-receptors: yohimbine. w in anaphylactic reaction, cardiac arrest, bronchos- w non-selective, e.g. phentolamine. pasm. ... see Adenosine triphosphate and diphosphate Phosphorylation Protein kinase of enzymes + other proteins Adrenal gland. Situated ... Clonidine and w labetalol and carvedilol have a- and b-receptor blocking other a2-receptor agonists (e.g. dexmedetomidine) have ...
Caffeine is a natural alkaloid methylxanthine that acts as a nonselective antagonist of adenosine receptors, with A1 antagonism ... with beta 1 agonist activity resulting in tachycardia and beta 2 agonist activity resulting in peripheral vasodilation and ... Caffeine exhibits ideal characteristics to be dialyzed, including low protein binding (36%), low molecular size (194), and a ... triggering seizures and A2 antagonism triggering cerebral and coronary vasoconstriction. Caffeine also inhibits ...
Agonist photoaffinity labeling of A1 adenosine receptors: Persistent activation reveals spare receptors (1986) ... Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed ... 1-DeazaNECA (10) proved tobe a nonselective agonist at both subtypes of the adenosine receptor. It is about 10-fold less active ... In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart ...
Inhibition of Nitrobenzylthioinosine-Sensitive Adenosine Transport by Elevated D-Glucose Involves Activation of P2Y2 ... Vassort G. Adenosine 5 -triphosphate: a P2-purinergic agonist in the the nucleotides, ATP and UTP of mitogen-activated protein ... theunaffected by the nonselective P2 purinoceptor antagonist inhibition of adenosine transport by high D-glucose, ATP,PPADS, ... Ali-quots (100 L) of M199 collected at the beginning (time 0) or at colocalized with A1 nucleoside receptors in the human ...
PBMCs were incubated with Ado receptor agonists and antagonist, and measurements were made after 30, 60, and 120 min as ... but these techniques are difficult to apply to low-density G protein-coupled receptors such as adenosine receptors. However, by ... 1996) Double tagging recombinant A1- and A2A-adenosine receptors with hexahistidine and the FLAG epitope. Development of an ... 1989) showed that radioligand binding to A2 receptors dramatically increases during monocyte differentiation in vitro. ...
Immunoprecipitation of A1 adenosine receptor-GTP-binding protein complexes in ciliary epithelial cells. Invest Ophthalmol Vis ... epinephrine is a nonselective adrenergic agonist that can activate both α- andβ -adrenergic receptors. Although the signal ... l-Epinephrine, adenosine A1 antagonists 8-(p-sulfophenyl)theophyline (8-SPT), adenosine A2 antagonists 3,7-dimethyl-l- ... Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol. 1986;29:331-346. [ ...
Agonist activity of 2- and 5′-substituted adenosine analogs and their N6-cycloalkyl derivatives at A1- and A2-adenosine ... and the ADORA1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nmol/L). Cells were lysed. Protein ... This may be due to nonselective binding of CPA to ADORA2A and ADORA2B receptors that are abundantly expressed on HEK293 cells ( ... The adenosine A1 receptor (Adora1) is a G-protein coupled receptor (GPCR) that is involved in maintaining glucose homeostasis ...
... induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X ... induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X ... However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, ... However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, ...
... which requires the adenosine A2 receptor (no A1 receptors are present in this cell line; A. S. Gordon and I. Diamond, ... coincubated cells transfected with the CRE-luciferase plasmid with ethanol and the nonselective adenosine receptor antagonist ... 2001) Ethanol acts synergistically with a dopamine agonist to cause translocation of PKC. Mol Pharm 59:153-160. ... which activates adenosine A2 receptors and increases intracellular cAMP levels (Nagy et al., 1991). The adenosine receptor ...
A.sub.2a receptor antagonists in particular are provided to enhance imm ... Described are uses of A.sub.2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses ... 1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and ... partial agonists at the receptor. In certain instances, non-selective agonists are also useful. Nonselective adenosine receptor ...
... whereas nonselective opioid receptor antagonist naloxone had no effect on it, the adenosine A1 receptor, rather than opioid ... Gels from cortex (A1 and B1), hippocampus (A2 and B2), and striatum (A3 and B3) have been shown. The molecular weight (MW) ... Involvement of Adenosine A1 Receptors and Regulator of G Protein Signaling Proteins. When rats were injected with DPCPX (1 mg/ ... in acute transient cerebral ischemia through activating adenosine A1 receptor in a manner different from its classic agonists ( ...
Action through Adenosine Receptors. There are different types of adenosine receptors labelled A1, A2a, A2b, and A3. Caffeine ... I. Biaggioni, S. Paul, A. Puckett, and C. Arzubiaga, "Caffeine and theophylline as adenosine receptor antagonists in humans," ... channels and the nonselective cation channel in the cell membrane begins. Caffeine directly activates the nonselective cation ... J. Á. Gómez-Ruiz, D. S. Leake, and J. M. Ames, "In vitro antioxidant activity of coffee compounds and their metabolites," ...
AC = adenylyl cyclase; A1, A2 = adenosine receptor subtypes; 1, 1, subunit with receptor 2 = adrenergic receptor subtypes; C = ... SKF-82958 is a pharmacologically selective D1 receptor agonist.) SCH-23390 is a D1/D5 receptor antagonist. There are likely ... dopamine1 receptor; D5 = dopamine5 receptor; ER = estrogen receptor; GR = glucocorticoid receptor; GRK = G protein-coupled ... Other clinically used inhibitors of MAO are nonselective and thus likely elevate the levels of DA, norepinephrine, and ...
A1 Adenosine Receptor Antagonists L971 Bg9928 Fk838 And Wrc0571 Last Updated on Mon, 15 Feb 2016 , Oral Bioavailability ... compound 5 was synthesized by exploring the SAR studies on N-ethyl carboxamide adenosine (NECA), a non-selective AR agonist 38 ... protein synthesis, electron transport, protein lipid modification for membrane anchoring and intracellular signaling (via ... Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a 50-kDa calcium-insensitive lipase produced predominantly by macrophages ...
A1 antagonist. Vasodilation fall in bp Less reflex tachy. Co decreases. Get postural hypotension Decrease LDL and increase hdl ... Non selective beta agonist. Less susceptible to uptake 1 and Mao Cardiogenic shock. Can get reflex tachycardia and ... Dopamine 2 receptor antagonist. Acts at ctz and increase gi motility and emptying. Cancer chemo, uraemia and go disorders More ... Less active at a1 more active on a2. Use for renal/cerebrovascular insufficiency or pregnant ...
... a2-adrenoreceptor, 5-HT1A, adenosine A1, GABAb, p- 8-, and K-opioid, and somatostatin receptors. The GIRK2 (Kir 3.2) channel is ... receptors and the often-disparate effects of receptor agonists and antagonists in animal models of anxiety SSRIs and the 5-HT1A ... Prior to the generation of 5-HT2C receptor-deficient mice, studies with nonse-lective agonists had suggested potential roles ... G protein-coupled receptors of many classes) and ionotropic receptors for amino acid neurotransmitters (i.e., y-amino butyric ...
In addition, theophylline is a potent non-selective inhibitor of adenosine receptors (primarily A1 and A2) at therapeutic ... Montelukast and zafirlukast are selective leukotriene receptor antagonists that specifically block the CysLT1 receptor, ... The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br J Pharmacol 2013; ... The protein binding is modest (30%) and it is extensively distributed in tissues and phagocytic cells such as macrophages and ...
... a β2-adrenoceptor antagonist, (−)-isoproterenol, a β-adrenoceptor agonist, and Rp-cyclic adenosine monophosphorothioate (Rp- ... including the A2 cell group) and caudal ventrolateral medulla (including the A1 cell group) (Woulfe et al., 1990; Forray et al ... To determine the receptor subtype, the effects of intra-vBNST injection of betaxolol (β1-selective antagonist) or ICI118,551 (β ... Effect of intra-vBNST injection of nonselective β-adrenoceptor antagonist on F-CPA. To determine the role of intra-vBNST β- ...
... shrinkage triggered by the non-selective P-1 adenosine agonist was blocked by the A3AR-selective antagonists (139). Metabolic ... A1;a2;:::;ak: Otherwise,considerthefirstnumberb1 62fa1;a2;:::;akgthatisnotfixed pivo. et al.. point automatic calculator pivot ... Interleukin-1 Receptor Type I The first studies on the specific receptor for IL-1a and IL-1ß were based on the identification ... Kondratyev K. Gapped BLAST and PSI-BLAST: A new gener- ation of protein database search programs. ...
  • 1. Inhibition of Nitrobenzylthioinosine-Sensitive Adenosine Transport by Elevated D-Glucose Involves Activation of P2Y2 Purinoceptors in Human Umbilical Vein Endothelial Cells Jorge Parodi, Carlos Flores, Claudio Aguayo, M. Isolde Rudolph, Paola Casanello, Luis SobreviaAbstract-Chronic incubation with elevated D-glucose reduces adenosine transport in endothelial cells. (slideshare.net)
  • Our findings demonstrate that inhibition of adenosine transport via hENT1 in endothelial cells cultured in 25 mmol/L D-glucose could be due to stimulation of P2Y2 purinoceptors by ATP, which is released from these cells in response to D-glucose. (slideshare.net)
  • In both phases, inhibition of cAMP-dependent protein kinase A (PKA) activity prevented ethanol-induced CRE-mediated luciferase expression. (aspetjournals.org)
  • This mechanism is distinct from PDE and adenosine receptor inhibition. (statpearls.com)
  • Binding of the endogenous ligand acetylcholine to the M 5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. (wikidoc.org)
  • Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. (bvsalud.org)
  • This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein. (bvsalud.org)
  • It's been proven that pharmacological inhibition of CDK9 by flavopiridol led to reduced AR transcription and proliferation prices, that are additional potentiated by AR antagonist . (angiogenesis-blog.com)
  • When the G-protein was included in the PLD assay, a strong dosage-dependent inhibition of the PLD activity was observed. (embl-heidelberg.de)
  • In vitro enzyme inhibition studies showed that the mixture of lanceolitols A1-A7 inhibited by 58.56% phospholipase A2 from bee venom, while the mixture of lanceolitols B1-B7 was cyclooxygenase-2 (COX-2) inhibitors (IC50 = 237 microM). (apitoxina.cl)
  • In summary, A 1 receptor-regulator of G protein signaling-K ATP signaling, arachidonic acid cascade, nitric oxide system, markers of neuronal damage, mitochondrial damage-related molecules, and the mitogen-activated protein kinase and nuclear factor-κB pathway are associated with the mechanisms of PF preconditioning. (aspetjournals.org)
  • In the present study, we investigated the involvement of the β-adrenoceptor-protein kinase A (PKA) signaling pathway within the BNST, in particular, within the ventral part of the BNST (vBNST), in pain-induced aversion in male Sprague Dawley rats. (jneurosci.org)
  • β-Adrenoceptors couple to adenylate cyclases to activate a protein kinase A (PKA), but no direct evidence exists for the involvement of the β-adrenoceptor-PKA signaling pathway in the affective component of pain. (jneurosci.org)
  • however, stimulation of this receptor is known to effectively decrease cyclic AMP levels and downregulate the activity of protein kinase A (PKA). (wikidoc.org)
  • 1996). "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. (wikidoc.org)
  • Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase α (G6Pase-α), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ζ (PKCζ) were assessed by western blot analysis. (bvsalud.org)
  • Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10⁻⁴ M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A1 receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α₁-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. (bvsalud.org)
  • Various kinase inhibitors, especially inhibitors of cell cyclin-dependent kinase (rescovitine), rho and Ca2+-dependent protein kinase (Y-27632), tyrosine kinase (tyrphostin AG879), phosphatidylinositol 3-kinase (bisindolylmaleimide I, BIM I), and Ca2+/calmodulin kinase (chelerythrine), strongly inhibited collagen gel contraction. (omicsonline.org)
  • TGF- signaling is set up by ligand binding to a transmembrane receptor with intracellular serine/threonine kinase activity, referred to as TGF- receptor-II (TR) (15). (conferencedequebec.org)
  • Upon ligand binding, TRII phosphorylates and stimulates the serine/threonine kinase activity of TR, also buy NP118809 called activin receptor-like kinase 5 (ALK5). (conferencedequebec.org)
  • Therefore, the increased proteins concentrations result in a FLJ34064 rise in kinase activity of the CDK9/cyclin T1 complicated. (angiogenesis-blog.com)
  • Included in these are PSD?95/Disk Huge/Zonula occludens-1 (PDZ) domains containing proteins from the membrane-associated guanylate kinase (MAGUK) family . (immune-source.com)
  • Palmitoylation of rPLD1 is not necessary for catalytic activity, since N-terminal truncation mutants lacking the first 168 or 319 amino acids exhibit high basal activity although they cannot be stimulated by protein kinase C (PKC). (embl-heidelberg.de)
  • Quiescent CHO-A1fos cells had been incubated using the indicated concentrations of PKC inhibitor, 3 nM [3H]DPCPX and where indicated 10 kinase assays demonstrated that treatment of CHO-A1 cells with PDBu (1 as assessed by autophosphorylation ((Amount 10). (conferencedequebec.org)
  • The lack of selective M5 receptor ligands is one of the main reasons that the medical community has such a limited understanding of the M5 receptors effects as the possibility that any and/or all effects of non-selective ligands may be due to interactions with other receptors can not be ruled out. (wikidoc.org)
  • Activation of DP 2 by PGD2 or other cognate receptor ligands has been associated with certain physiological and pathological responses, particularly those associated with allergy and inflammation, in animal models and certain human diseases. (wikipedia.org)
  • G protein-coupled receptors (GPCRs) such as DP 2 are integral membrane proteins that, when bound by their cognate ligands (or, in some cases, even when not ligand-bound and thereby acting continuously in a constitutive manner {see Receptor (biochemistry)#Constitutive activity }), mobilize one or more types of Heterotrimeric G proteins . (wikipedia.org)
  • 2-(4,5-dihydro-1H-imidazol-2-yl)indazole (indazim) derivatives as selective I(2) imidazoline receptor ligands. (isni.org)
  • We established that endothe-reduce the NBMPR-sensitive adenosine transport associated lial cells express the hENT1 isoform of nucleoside transporterswith increased protein levels and the activity of endothelial and that incubation with 25 mmol/L D-glucose leads to inhibitionNO synthase, intracellular Ca2 , PKC, and mitogen-activated of adenosine transport by a mechanism that involves the activa-protein kinases p42/p44mapk.6,10 Thus, hENT1 adenosine trans- tion of P2Y2 purinoceptors. (slideshare.net)
  • These receptors fall into families, based primarily on the way in which they generate the intracellular signals that give rise to the particular functional responses. (axonmedchem.com)
  • This changed receptor efficiency might derive from unusual receptor connections with regulatory protein, consistent with prior results indicating that 5-HT2A receptors associate with multiple intracellular protein, which are crucial for the legislation of their useful position [18, (immune-source.com)
  • A1 receptors are implicated in sleep promotion by inhibiting wake-promoting cholinergic neurons in the basal forebrain. (wikipedia.org)
  • In keeping with this hypothesis, we previously showed that disrupting the connections between vertebral 5-HT2A receptors and linked PDZ protein by an interfering peptide in a position to transduce into vertebral neurons after intrathecal shot, inhibited thermal and mechanised hyperalgesia and improved fluoxetine-induced analgesia . (immune-source.com)
  • Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, did not alter this effect. (bvsalud.org)
  • CDK9 regulates the androgen receptor through S81 phosphorylation which is an essential part of regulating not merely its transcriptional activity, also for prostate cancers cell development . (angiogenesis-blog.com)
  • BACKGROUND: Several types of receptors are found at neuromuscular presynaptic membranes. (bvsalud.org)
  • The effects of D-glucose and nucleotides on the number and activity of hENT1 and hENT1 mRNA were blocked by reactive blue 2 (nonspecific P2Y purinoceptor antagonist), suramin (G s protein inhibitor), or hexokinase but not by pyridoxal phosphate-6-azophenyl- 2 ,4 -disulfonic acid (nonselective P2 purinoceptor antagonist). (slideshare.net)
  • complicated, CDK9 interacts also with the androgen receptor (AR) to improve transcription activity . (angiogenesis-blog.com)
  • Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided. (organic-reaction.com)
  • However, it is possible that an imidazoline receptor located at another ocular or extraocular site may contribute to the ocular hypotensive actions of those clonidine-like imidazolines that interact with both a2-adrenoceptors and imidazoline I1-receptors, such as moxonidine. (pharmacologicalsciences.us)
  • The PGS/PGs/PG receptors signaling pathway in chronic aluminium gluconate-overloaded rat hippocampus is disturbed, which may be involved in the mechanism of aluminium neurotoxicity. (biomedcentral.com)
  • The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptor-benzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. (bvsalud.org)
  • Antagonizing the anticonvulsant effect of ethanol using drugs acting at the benzodiazepine/GABA receptor complex. (isni.org)
  • Assessment of GABA(A)benzodiazepine receptor (GBzR) sensitivity in patients on benzodiazepines. (isni.org)
  • Recently, our laboratory found that PF could produce a dose-dependent decrease in both neurological impairment and infarct volume in acute transient cerebral ischemia through activating adenosine A 1 receptor in a manner different from its classic agonists (Liang et al. (aspetjournals.org)
  • To understand the role of A 2A Rs in the regulation of immune response, we investigated the expression levels of this receptor in different functional lymphocyte subsets. (aspetjournals.org)
  • Both proteins were functional in biochemical assays. (embl-heidelberg.de)
  • liberal download nihonsense is the A2 dinner for 4X database, though additional technician generically was here discharged here of the modern Auditor photography and functional origin page beaten by intestinal resource. (qarty.eu)
  • This anti-hyperalgesic impact involves vertebral 5-HT2A receptors and GABAergic interneurons since it is normally abolished with a 5-HT2A antagonist (M100907, 150 ng/rat, intrathecally) and a GABAA antagonist, (bicuculline, 3 g/rat, intrathecally). (immune-source.com)
  • Feasible Rabbit Polyclonal to SSBP2 adjustments in the amount of 5-HT2A receptors and its own associated PDZ proteins PSD-95 upon irritation induction had been quantified by Traditional western blotting in dorsal horn spinal-cord. (immune-source.com)
  • The ensuing pellet was resuspended in 600 may Rabbit Polyclonal to CBLN2 be the agonist focus and may be the Hill coefficient. (conferencedequebec.org)
  • It is a member of the class of prostaglandin receptors which bind with and respond to various prostaglandins . (wikipedia.org)
  • DP 2 along with Prostaglandin DP1 receptor are receptors for prostaglandin D2 (PGD2). (wikipedia.org)
  • In order to explore the mechanism of aluminum neurotoxicity and the importance of COX2 downstream signaling pathways to chronic brain damage, the present study was designed to simultaneously observe the prostaglandin (PG) contents, and the expressions of PG synthases and PG receptors of hippocampus in a rat model induced by chronic administration of aluminium gluconate. (biomedcentral.com)
  • Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I. encodes a small myristoylated protein required for optimal viral replication and AIDS pathogenesis [1, (angiogenesis-blog.com)
  • The system in charge of the anti-angiogenic properties of both flavopiridol and SNS-032 possess therefore been partly ascribed to down-regulation of both mRNA and proteins degrees of VEGF, the strongest tumour angiogenic aspect [56; (angiogenesis-blog.com)
  • The DP1, EP2, IP, mPGES-1, EP4, PGIS and TXAS mRNA expressions, and the DP1, EP2 and IP protein expressions significantly increased in the Al-treated hippocampus, while the EP3 and FP mRNA and protein expressions and the TP mRNA expression decreased. (biomedcentral.com)
  • A1 receptors are also present in smooth muscle throughout the vascular system. (wikipedia.org)
  • Laboratorio de Investigación en Función Vascular, Departamento de Investigaciones, Fundación CardioInfantil-Instituto de Cardiología, Carrera 13b no. 163-85, Torre A, Piso 3. (hindawi.com)
  • In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. (hindawi.com)