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.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.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.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 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.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 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.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Ca(2+) Mg(2+)-ATPaseAdenosine 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.Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.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.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).Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Sodium-Potassium-Exchanging ATPase: An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Calcium-Transporting ATPases: Cation-transporting proteins that utilize the energy of ATP hydrolysis for the transport of CALCIUM. They differ from CALCIUM CHANNELS which allow calcium to pass through a membrane without the use of energy.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Kinetics: The rate dynamics in chemical or physical systems.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)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.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.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.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.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.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.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.2-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.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.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.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.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)Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.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.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Adenine NucleotidesAdrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.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.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)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.Mice, Inbred C57BLHistamine 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.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.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.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.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).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)Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR 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.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.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.Piperidines: A family of hexahydropyridines.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.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.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.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.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.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.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.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.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.Colforsin: 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.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.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.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.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)Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.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.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.Quinpirole: A dopamine D2/D3 receptor agonist.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.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.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.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.TriazolesNicotinic 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.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.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.Benzazepines: Compounds with BENZENE fused to AZEPINES.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.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.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic 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)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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.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)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).Behavior, Animal: The observable response an animal makes to any situation.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Piperazines8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 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.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.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.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.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.PyrrolidinesAmino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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.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.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.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.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.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.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.Deoxyadenosines: Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.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)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.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.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.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.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.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.Nucleoside Transport Proteins: Proteins involved in the transport of NUCLEOSIDES across cellular membranes.Purinergic P2Y Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.Purinergic Agonists: Compounds that bind to and activate PURINERGIC RECEPTORS.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.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Pertussis 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.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.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).Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Heart: The hollow, muscular organ that maintains the circulation of the blood.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.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.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.-.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Purinergic P2X Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.Animals, Newborn: Refers to animals in the period of time just after birth.Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.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)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.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)MorpholinesBenzoxazines: OXAZINES with a fused BENZENE ring.Depression, Chemical: The decrease 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.Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
AdenosineAll adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A ... Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. When ... since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole ( ...
The CB1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, ... A likely candidate for this function is the heterodimer of CB1 and adenosine 2a. Through an opposing mechanism of action (A2A ... Endogenous CB1 antagonist and CB2 agonist) Rimonabant Taranabant Lipoxin A4 - endogenous, PAM ZCZ-011 - PAM Pregnenolone - ... Repeated administration of receptor agonists may result in receptor internalization and/ or a reduction in receptor protein ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry. 46 (7 ... Cristalli G, Lambertucci C, Taffi S, Vittori S, Volpini R (2003). "Medicinal chemistry of adenosine A2A receptor agonists". ... "The novel adenosine A2a receptor antagonist ST1535 potentiates the effects of a threshold dose of L-DOPA in MPTP treated common ... "Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats". ...
IN the visual system, cannabinoids agonist induce a dose dependent modulation of calcium, chloride and potassium channels. This ... A likely candidate for this function is the heterodimer of CB1 and adenosine 2a. Through an opposing mechanism of action (A2A ... 4 A5,4 16.28 cM. Start. 33,924,593 bp[2]. End. 33,948,831 bp[2]. ... Agonist 0.28 nM Agonist Synthetic [43]. AM-1235 1.5 nM Agonist ... Full agonist 480 nM Full agonist Endogenous Tetrahydrocannabinol 10 nM Partial agonist 24 nM Partial agonist Phytogenic [42][42 ...
... is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A2A receptor. ... increasing the effect of THC in a dose-dependent manner. Despite this, the available evidence in humans suggests no significant ... It has also been shown to act as a 5-HT1A receptor partial agonist, and this action may be involved in the antidepressant, ... "Cannabis à faible teneur en THC et CBD". bag.admin.ch. Retrieved May 20, 2017. ...
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Low doses can result in psychological effects of "mild euphoria, alertness, and enhanced cognitive performance"; higher doses ... Diagnosis according to the DSM-5 is dependent on various criteria. Patients must present symptoms of either panic attacks or ... Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors ...
"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 ... Toxic doses, over 10 grams per day for an adult, are much higher than typical doses of under 500 milligrams per day. A cup of ... The LD50 of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150 to 200 milligrams per ...
... activation of Ca2+/calmodulin-dependent protein kinase II can be cAMP dependent or independent.[15] ... are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors. ... Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working ... increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP).[6] ...
... is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and ... This control involves, at least in part, the DP2-dependent activation of the male germ cell marker Nanos2 and the inhibition of ... Sidharta PN, Diamant Z, Dingemanse J (2014). "Single- and multiple-dose tolerability and pharmacokinetics of the CRTH2 ... Adenosine (A1. *A2A. *A2B. *A3). *P2Y (1. *2. *4. *5. *6. *8 ... "Prostanoid Receptors: DP2". IUPHAR Database of Receptors and ...
LTD4 in stimulating GPR99-bearing cells and GPR99-deficient mice exhibit a dose-dependent loss of vascular permeability ... discovery of a subtype selective agonist". Mol. Pharmacol. 58 (6): 1601-8. PMID 11093801.. ... Adenosine (A1. *A2A. *A2B. *A3). *P2Y (1. *2. *4. *5. *6. *8 ... Receptor[edit]. CySLTR2 mRNA is co-expressed along with CysLRR1 ... leukotriene receptor activity. • cysteinyl leukotriene receptor activity. • galanin receptor activity. Cellular component. • ...
This is called a dose-dependent effect. Building on this, it was found that there are growth hormone secretagogue receptors in ... This is called constitutive activity, and it means that the receptor is always "on," unless acted on by an inverse agonist. ... Adenosine (A1. *A2A. *A2B. *A3). *P2Y (1. *2. *4. *5. *6. *8 ... "Ghrelin Receptor". IUPHAR Database of Receptors and Ion ... dopamine receptor type 2 (DRD2),[11] melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT2c receptor).[11] See ...
Each type of adenosine receptor has different functions, although with some overlap.[3] For instance, both A1 receptors and A2A play roles in the heart, regulating ...
Adenosine monophosphate deaminase deficiency type 1, also called myoadenylate deaminase deficiency (MADD), is a recessive genetic metabolic disorder that affects ...
The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled ...
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it. This protein is a member of the G protein-coupled ...
5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is an intermediate in the generation of inosine monophosphate. AICAR is an analog of adenosine ...
Diprophylline (INN) or dyphylline (USAN) (trade names Dilor, Lufyllin), is a xanthine derivative with bronchodilator and vasodilator effects. It is used in the treatment of respiratory disorders like asthma, ...
Adenosine diphosphate (or ADP) is the chemical that plants make ATP from, during photosynthesis. A chemical compound that can be converted to ATP with the addition of one phosphate group. ...
The pre-Bötzinger complex (preBötC) is a cluster of interneurons in the ventral respiratory centre of the medulla of the brainstem. This complex has been proven to be essential for the generation of respiratory rhythm in mammals. The exact mechanism of the rhythm generation ...
Dipyridamole (trademarked as Persantine and others) is a medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a ...
Bevan N, Butchers PR, Cousins R, Coates J, Edgar EV, Morrison V, Sheehan MJ, Reeves J, Wilson DJ (2007). „Pharmacological characterisation and inhibitory effects of ...
The ATP molecule is very versatile, meaning that it can be used for many things. Energy is stored in its chemical bonds. When ATP binds with another phosphate, energy is stored that can be used later. In other words, when a bond is made, energy is stored. ...
Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT (August 2007). "Effects of multiple oral doses of an A1 adenosine antagonist, ...
Johnson, M., Kaye, M.A.G., Hems, R. and Krebs, H.A. (1953). „Enzymic hydrolysis of adenosine phosphates by cobra venom". Biochem. J. 54: 625-629. PMID 13058963 ...
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A ... Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. When ... since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole ( ...
Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens | Journal of Neuroscience... blockade of adenosine A1 receptors also may play a relevant role. At the dose used in the present study, the A2A receptor ... 1992) Caffeine-induced behavioral stimulation is dose-dependent and associated with A1 adenosine receptor occupancy. ... 1989) Inhibition of nigrostriatal release of dopamine in the rat by adenosine receptor agonists: A1 receptor mediation. ... and the adenosine A2A antagonist 5-amino-7-(2-phenylethyl)2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH ...
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression | JEM... by allogeneic cells in culture was substantially inhibited in a dose-dependent fashion in the presence of A2A-specific agonists ... A2a, A2B, and A3. Adenosine is a potent inhibitor of T cell responses (19), and the A2A receptor has been identified as the ... Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A- ... including A2A (18). Seminal, important genetic data indicate that adenosine, which is operative via the A2A adenosine receptor ...
The A1AR agonist, N6-cyclopentyladenosine, inhibited heart rates in a dose-dependent manner (half-maximal effective ... In contrast, A2a and A2b receptor activation did not alter heart rates, and activation of A3 receptors produced modest declines ... In contrast, A2a and A2b receptor activation did not alter heart rates, and activation of A3 receptors produced modest declines ... In contrast, A2a and A2b receptor activation did not alter heart rates, and activation of A3 receptors produced modest declines ...
Adenosine-5'-(N-ethylcarboxamide)
- NECA
Summary Report | CureHunterA stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity. ... induced dose dependent catalepsy. ". 01/01/1993 - "The A1 adenosine antagonist 8-phenyltheophylline (8-PT) potentiated ... 06/01/1991 - "Prostaglandin E1, like NECA, also caused retinal vasodilation and hemorrhages. ". 06/01/1991 - "These data ... Adenosine A2A Receptor (Adenosine A2A Receptors) 6. Pentylenetetrazole (Metrazol) 7. Adenosine A1 Receptor ...
Research in Pharmaceutical Sciences : Table of ContentsThe expression pattern of all adenosine receptor subtypes are as follow; A2b , A1 , A2a , A3 in untreated MCF-7 cells. Obtained ... MTT assay showed that nardosinen notably inhibited cell proliferation in a dose-dependent manner in MCF-7 breast cancer cells. ... MCF-7 cells were used to treat with agonist and antagonist of estrogen and then the mRNA expression of adenosine receptor ... The gene expression of adenosine receptor subtypes were detected by real time RT-PCR. The results of MTT assay showed that E2 ...
Managing Intraocular Pressure: Innovation in Glaucoma Management | IntechOpenA2A and A3 AR agonists have shown to increase Ca2+ in the cells of the SC and to diminish TM cell volume [40]. Outflow ... Adenosine receptors (ARs) belong to the family of G protein-coupled receptors (GPCR) [37]. Four subtypes of AR have been ... Administration of trabodenoson resulted in a dose-related IOP reduction; the highest dose tested achieved a statistically ... The treatment uses an AdV vector for the expression of p21 WAF-1/Cip1, a potent cyclin-dependent kinase inhibitor to reduce ...
Frontiers | Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity | Public Health... showed significant increase in A2A receptor signaling and in the capability, upon treatment with adenosine agonists, to inhibit ... Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol (2007) ... Whereas A1 and A3 ARs inhibit adenylate cyclase activity and, therefore, decrease cAMP production, stimulation of A2A and A2B ... Individuals were stratified according to the ELF-EMF exposure dose in low (,0.2 μT) and high (,0.2 μT) exposed workers and NK ...
Aging | Tyrosine nitrations impaired intracellular trafficking of FSHR to the cell surface and FSH-induced Akt-FoxO3a signaling...Increased levels of peroxynitrite, tyrosine nitrations of FSH receptor (FSHR) and apoptosis were obviously detectable with ... human histamine H1 receptor; AA3R, human adenosine A3 receptor; AA2A, human adenosine A2a receptor; AA2B, human adenosine A2b ... Rescue of oligomerization-dependent defective receptor expression by using cognate decoys. Mol Cell Endocrinol. 2010; 321:112- ... Next, we found that PN dose-dependently caused the tyrosine nitrations and proteasome-mediated degradations of FSHR in vitro. ...
![Full text] Current treatments for acute heart failure: focus on serelaxin | RRCC](data:image/png;base64,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)
Full text] Current treatments for acute heart failure: focus on serelaxin | RRCCA2a, A2b, and A3 receptors.43,44 In the kidney, adenosine activates the A1 receptor to cause vasoconstriction of cortical ... Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like ... Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal. 2012;8(Suppl 1):91-99. ... The PROTECT pilot study: A randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist ...
IFN-γ Prevents Adenosine Receptor (A2bR) Upregulation To Sustain the Macrophage Activation Response | The Journal of ImmunologyExtracellular adenosine can signal through four receptors, designated A1, A3, A2a, and A2b (19). All adenosine receptors are G ... On unprimed cells, adenosine suppressed LPS-induced TNF-α in a dose-dependent manner, indicating that macrophages are sensitive ... Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. ... Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. ...
The CB1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, ... A likely candidate for this function is the heterodimer of CB1 and adenosine 2a. Through an opposing mechanism of action (A2A ... Endogenous CB1 antagonist and CB2 agonist) Rimonabant Taranabant Lipoxin A4 - endogenous, PAM ZCZ-011 - PAM Pregnenolone - ... Repeated administration of receptor agonists may result in receptor internalization and/ or a reduction in receptor protein ...
Adenosine inhibits IL-12 and TNF-α production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 14:2065 ... Adenosine and adenosine receptor agonists also inhibit macrophage inflammatory responses, including the release of TNF-α (10, ... Inhibition of TNF-α expression by adenosine: role of A3 adenosine receptors. J. Immunol. 156:3435. ... Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-γ release while increasing IL-4/ ...
The Role of Extracellular Adenosine Generation in the Development of Autoimmune DiseasesThe final aim is to consider the role of adenosinergic ectoenzymes and ADO receptors as novel therapeutic targets for selected ... which suppresses the immune responses by interacting with specific receptors expressed by immune effector cells. ADO is ... "Inhibition of experimental auto-immune uveitis by the A3 adenosine receptor agonist CF101," International Journal of Molecular ... ADO acts as a danger signal, by activating specific ADO receptors (ADOR), namely, A1, A2A, A2B, and A3, different in function ...
Myocardial postconditioning: anesthetic considerations89 The protective effects could be blocked by the nonselective adenosine receptor antagonist, 8SPT,90 and by A2a and A3 ... Lecour and colleagues,98 have demonstrated that exogenous TNFα, in a dose and time dependent manner, could mimic ischemic ... Two selective delta 1 opioid receptor agonists (TAN 67 and BW373U86) and morphine were initially shown to augment isoflurane ... Indeed, recent reports have addressed that adenosine A2a and A2b receptors are responsible for the protection granted by PostC. ...
Four subtypes of metabotropic P1 receptors have been cloned and named A1, A2A, A2B, and A3 [25, 27]. The P2 receptors exist in ... but not by a P2X receptor antagonist (Ip5I). Furthermore, selective P2Y2 agonist-(2-Thio-UTP-), P2Y2/P2Y4 agonist-(UTPγS-), and ... in addition to smooth muscle P2X1 receptor-mediated vasoconstriction, Up4A showed concentration-dependent P2Y2 receptor- ... single dose versus step-up doses). Future experiments need to be performed to address this question. ...
The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review |...Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ... irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, ... on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load ... irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, ...
Sleep deprivation - ScholarpediaAdenosine A2a receptor agonists incite VLPO neurons to express Fos protein, and also promote sleep in rats; these, and other ... These changes are somewhat dependent on the time of measurement post-SD; there is a rebound increase of cortisol before sleep ... Van Dongen HP, Maislin G, Mullington JM, Dinges DF (2003) The cumulative cost of additional wakefulness: dose-response effects ... Aviat Space Environ Med 75:A4-14. *Mignot E (2004) Sleep, sleep disorders and hypocretin (orexin). Sleep Med 5 Suppl 1:S2-8. ...
Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β2-Adrenoceptors to Gs and Gi Proteins in Mouse...2009) Agonist dose-dependent phosphorylation by protein kinase A and G protein-coupled receptor kinase regulates β2 ... 2007) Protective roles of adenosine A1, A2A, and A3 receptors in skeletal muscle ischemia and reperfusion injury. Am J Physiol ... the Gi-dependent effects of clenbuterol and cAMP were mimicked by adenosine and inhibited by adenosine receptor antagonists CGS ... Indirect cross-talk of Gs-coupled β2-AR and Gi-coupled adenosine receptors. Activation of β2-AR by agonist induces a Gs- ...
However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, ... this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors ... this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors ... We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse ...
Adenosine... ) Routes of administration IntravenousATC codeC01EB10 (WHO)Legal statusLegal statusIn general: ℞ (Prescription only) ... Rapidly cleared from circulation via cellular uptakeProtein binding NoMetabolism Rapidly converted to inosine and adenosine ... Adenosine receptors[edit] Main article: Adenosine Adenosine receptor All adenosine receptor subtypes (A1, A2A, A2B, and A3) are ... "Anti-Inflammatory Preconditioning by Agonists of Adenosine Adenosine A1 Receptor". PLoS ONE. 3 (5): e2107. Bibcode:2008PLoSO... ...
Regadenoson - DrugBankRegadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining ... a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl ... It is a very weak agonist of the A1 adenosine receptor (Ki , 16.5 µM). Furthermore, it has negligible affinity to A2B and A3 ... Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining ...
Adenosine activates four subtypes of G protein-coupled adenosine receptors (ARs), A1/A2A/A2B/A3. Enprofylline, (compound B), is ... A2A,and A3 ARs, only few selective antagonists and no selective agonists are known for the A2B receptor. Therefore, a ... adenosine acting as a local modulator of adenosine receptors in the brain and other organs at therapeutically useful doses. ... endothelial-dependent vasodilation (See Martin, P.L., etal, J. Pharmacol Exp. Ther. 1993,265,248-253), and fluid secretion from ...
Extracellular purine metabolism and signaling of CD73-derived adenosine in murine Treg and Teff cells | Cell PhysiologyFour distinct subtypes of P1 receptors have been identified: adenosine A1, A2a, A2b, and A3 receptors (R) which are G protein ... A2a adenosine receptor agonist CGS21680 was 10 pM to 1 μM. ... B: dose-response curve of CGS21680 on IFN-γ release. Data are ... ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ ... Inhibition of adenosine-mediated IFN-γ release is due to A2a adenosine receptor activation.. Among the specific adenosine ...
The A2b adenosine receptor protects against vascular injury | PNASAlthough adenosine activates multiple receptor subtypes (A1, A2a, A2b, and A3 receptors), the adenylyl cyclase stimulatory A2a ... an in vivo model of smooth muscle cell proliferation revealed that an A2 receptor agonist, 2-octynyladenosine, inhibited ... Ten-week-old WT or A2bAR KO male mice were irradiated with a total dose of 12.5 Gy from a 137Cs source. On the day of ... which is mediated via the A2bAR in a cAMP-dependent pathway (7). Interestingly, ...
AntagonistsExtracellular adenosineAbstractSubtypes of G proteinPharmacologicalImmunosuppressive adenosineEffect of adenosineSuggest that adenosineProteinsSubtypeCD73CyclicPotentBlockade of adenosine receptorsStimulationMacrophagesExpression of adenosine receptorNECAInhibitionDopaminePurinergic receptorsData indicate that adenosineActivatesNucleoside adenosineMediateShow that adenosineIschemicMiceA2AR and A2BRMetabotropicAdenylylMurineTherapeuticRatsPhosphorylationProtein kinaseInducesMediatorsInhibitorInverse agonistPathwaysKinasePartial agonistsModulatorA2bRApoptosisMechanism
- The present invention provides compounds and pharmaceutical compositions that are selective antagonists of A2B adenosine receptors (ARS). (allindianpatents.com)
- The present invention relates to compounds and pharmaceutical compositions that are selective antagonists of A2B adenosine receptors (ARs). (allindianpatents.com)
- In recent years, the use of theophylline as a bronchodilator, for relief of asthma, has been supplanted by drugs of other classes, i.e., selective β2-adrenergic agonists, corticosteroids, and recently leukotriene antagonists. (allindianpatents.com)
- It has also been shown by LaNoue et al (U,S, Patent No. 6,060,481) that selective adenosine A2B antagonists are useful for improving insulin sensitivity in a patient. (allindianpatents.com)
- It has been reported that therapeutic concentrations of theophylline or enprofylline block human A2B receptors, and it has been proposed that antagonists selective for this subtype may have potential use as antiasthmatic agents. (allindianpatents.com)
- Recently Linden et al (U.S. Patent No. 6,545,002) have described a new group of compounds and pharmaceutical compositions that are selective antagonists of A2B adenosine receptors (ARs). (allindianpatents.com)
- Although adenosine receptor subtype-selective probes are available for the A1, A2A,and A3 ARs, only few selective antagonists and no selective agonists are known for the A2B receptor. (allindianpatents.com)
- Therefore, a continuing need exists for compounds that are selective A2B receptor antagonists. (allindianpatents.com)
- The present invention provides compounds that act as antagonists of A2B adenosine receptors. (allindianpatents.com)
- No highly selective agonists or antagonists for the M 5 receptor have been discovered as of 2018, but several non-selective muscarinic agonists and antagonists have significant affinity for M 5 . (wikidoc.org)
- Effects of Adenosine Receptor Antagonists on the In Vivo LPS-Induced Inflammation Model of Parkinson's Disease. (biomedsearch.com)
- Adenosine A 2A receptor antagonists emerged as a new promising non-dopaminergic therapy of Parkinson's disease (PD) (Schwarzschild et al. (biomedsearch.com)
- 2000 ). Presynaptically, A 2A receptor antagonists are able to potentiate D 2 receptor control of glutamatergic transmission which is dysfunctional in PD (Tozzi et al. (biomedsearch.com)
- 2007 ). A 2A adenosine receptor antagonists were shown to alleviate symptoms of PD in a number of behavioral studies in rodents and primates. (biomedsearch.com)
- In a rodent models of PD, A 2A adenosine receptor antagonists increased locomotor activity in MPTP-treated or reserpinized mice, reversed haloperidol-induced catalepsy in rats (Shiozaki et al. (biomedsearch.com)
- A 2A receptors modulate processes accompanying brain injury in animal models of several neurological disorders and recently a neuroprotective potential of A 2A receptor antagonists has been suggested (Chen et al. (biomedsearch.com)
- This review provides an overview of the medicinal chemistry and therapeutic potential of various agonists/partial agonists, antagonists and allosteric modulators of A1 AR, with a particular emphasis on their current status and future perspectives in clinical settings. (eurekaselect.com)
- A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR. (eurekaselect.com)
- A1 adenosine receptor agonists, antagonists, and allosteric modulators. (eurekaselect.com)
- Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia-HIF-1α signaling. (aacrjournals.org)
- however, medicines designed as -AR agonists or antagonists can activate option cell signalling pathways, using the potential to impact medical efficacy. (healthweblognews.info)
- Agonists performing at -ARs screen ligand-directed signalling, but many medications performing as cAMP antagonists can also activate signalling pathways central to cell success and proliferation or cell loss of life. (healthweblognews.info)
- At low agonist concentrations, the response is because of Gs activation, whereas at higher concentrations c-Src is certainly involved separately of both G proteins and arrestins (Sunlight (2007), On the severe, functionally selective ligands could be both agonists and antagonists at different features mediated with the same receptor. (healthweblognews.info)
- Therefore, we discussed in this review various receptors agonists, antagonists, activators and inhibitors which will have effects on cardiovascular system. (rroij.com)
- 5-HT1A receptor agonist-induced hypothermia in mice: reversal by 5-HT1A receptor antagonists. (healthweblognews.info)
- Microglial cells or rats were treated with or without lipopolysaccharide (LPS) in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. (freedomwares.ca)
- antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors. (wikipedia.org)
- In addition, both acid production and radioligand binding of adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas ligands for A 1 , A 2A , and A 3 adenosine receptors failed to abolish activation. (physiology.org)
- 3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists. (nih.gov)
- 2-aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists. (nih.gov)
- Ramatroban , vidupiprant, and Bay U3405 are non-selective (i.e. known to influence other receptors) antagonists of DP 2 . (wikipedia.org)
- Consequently, novel NK 1 receptor antagonists are now in use for the treatment of nausea and emesis , and are also being investigated for the treatment of anxiety and depression . (wikidoc.org)
- Open up in another window Amount 6 Aftereffect of CB1 and CB2 receptor antagonists over the antinociceptive aftereffect of p.o. (angiogenesis-blog.com)
- mGluR5 receptors are also expressed outside the central nervous system, and mGluR5 antagonists have been shown to be hepatoprotective and may also be useful for the treatment of inflammation and neuropathic pain. (wikidoc.org)
- In this study, we demonstrate that, following TLR stimulation, macrophages upregulate the adenosine 2b receptor (A2bR) to enhance their sensitivity to immunosuppressive extracellular adenosine. (jimmunol.org)
- In this study, we investigated the effect of IFN-γ on TLR-activated macrophages, and we reveal that IFN-γ sustains inflammatory macrophage activation by attenuating their sensitivity to extracellular adenosine. (jimmunol.org)
- ADO also has receptor-independent effects, because extracellular adenosine can cross the cell membrane and activate AMP-activated protein kinase (AMPK), adenosine kinase, and S-adenosyl homocysteine hydrolase pathways [ 2 ]. (hindawi.com)
- We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. (physiology.org)
- In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction and increased myocardial 3′-nitrotyrosine. (ahajournals.org)
- Recently, we demonstrated that genetic deletion of CD73 (an ectonucleotidase that produces extracellular adenosine) exacerbated myocardial hypertrophy and heart failure resulting from left ventricular (LV) pressure overload produced by transverse aortic constriction (TAC), 1 suggesting that endogenous extracellular adenosine can protect against maladaptive hypertrophy. (ahajournals.org)
- Hypoxia-driven accumulation of extracellular adenosine results in the generation of an immunosuppressive niche that fuels tumor development. (springer.com)
- Extracellular adenosine induces potent immunosuppressive effects, mainly mediated through four adenosine-binding G protein-coupled receptors: A1, A2A, A2B, and A3 ( 15 ). (aacrjournals.org)
- Because A2AAR protected tumors from incoming antitumor T cells ( 21 ), we hypothesized that extracellular adenosine generated by CD73 on tumor cells would impair antitumor immunity. (aacrjournals.org)
- In support of this approach are preclinical studies and findings that some human cancers are resistant to chemotherapies and immunotherapies due to the tumor-generated extracellular adenosine and A2AR on antitumor T and natural killer (NK) cells. (aacrjournals.org)
- The hypoxia-driven stabilization of HIF-1α transcription factor leads to CD39/CD73 ectoenzyme-mediated generation of extracellular adenosine, which signals through the G s -protein-coupled A2A and A2B adenosine receptors (A2AR and A2BR) and triggers the accumulation of intracellular cAMP. (aacrjournals.org)
- abstract = "A1 adenosine receptors (A1ARs) have been recently shown to be expressed in rodent embryonic hearts at very early stages of development. (elsevier.com)
- Adenosine activates four subtypes of G protein-coupled adenosine receptors (ARs), A1/A2A/A2B/A3. (allindianpatents.com)
- Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. (aspetjournals.org)
- Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy In: ed Protein Reviews. (eurekaselect.com)
- Furthermore, you'll be able to make use of tissues from genetically improved pets, and assess pharmacological modulation of agonist replies. (flora2world.com)
- The classic model of G protein-coupled receptor (GPCR) signaling, where receptors, G proteins, effector enzymes, and downstream signaling proteins float in a sea of phospholipids and interact with one another stochastically and generate a global signal via a second messenger, does not explain pharmacological reality. (aspetjournals.org)
- Thus, the pharmacological reality is that at least 20-30 of these receptors couple G α s , stimulate adenylyl cyclase (AC) activity, and promote cAMP production. (aspetjournals.org)
- The renewed interest in the adenosine A 2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. (physiology.org)
- Although preliminary, these results indicate that purinergic receptors are putative pharmacological targets that should be further explored in future studies. (biomedcentral.com)
- The metabotropic glutamate receptors are a family of G protein-coupled receptors , that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacological properties. (wikidoc.org)
- After TLR stimulation, macrophages alter their metabolism and release low levels of ATP, which is rapidly converted into immunosuppressive adenosine via CD39-mediated hydrolysis. (jimmunol.org)
- Downregulation of P2X7 and upregulation of CD73 in Treg after antigenic stimulation may be an important mechanism to maintain the ability of Treg to generate immunosuppressive adenosine. (physiology.org)
- Because the ecto-5′-nucleotidase activity of CD73 catalyzes AMP breakdown to immunosuppressive adenosine, we hypothesized that CD73-generated adenosine prevents tumor destruction by inhibiting antitumor immunity. (aacrjournals.org)
- One critical mechanism of cancer immune evasion is the generation of high levels of immunosuppressive adenosine within the tumor microenvironment. (biomedcentral.com)
- Babich V, Vadnagara K, Di Sole F (2015) Dual effect of adenosine a1 receptor activation on renal O2 consumption. (springer.com)
- Conclusions- Adenosine exerts protective effects on the overloaded heart, but the A 3 R acts counter to the protective effect of adenosine. (ahajournals.org)
- Additional studies suggest that adenosine induces apoptosis of human arterial smooth muscle cells, which is mediated via the A2bAR in a cAMP-dependent pathway ( 7 ). (pnas.org)
- In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A 2B receptors, suggest that adenosine receptors, specifically the G s -coupled A 2A and A 2B receptors, might provide such a target. (aspetjournals.org)
- Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. (ekja.org)
- Research suggests that the majority of CB1 receptors are coupled through Gi/o proteins. (wikipedia.org)
- Alternatively, in some rare cases CB1 receptor activation may be coupled to Gs proteins, which stimulate adenylate cyclase. (wikipedia.org)
- A1 and A3 receptors are coupled with G proteins of the Gi, Gq, and Go family, and their activation leads to the release of calcium ions from intracellular stores. (hindawi.com)
- In contrast, A2A and A2B receptors are coupled with G proteins Gs or Gq and activate adenylyl cyclase or phospholipase C. Moreover, all adenosine receptors activate mitogen-activated protein kinase (MAPK) pathways, which include extracellular signal regulated kinase 1 (ERK1), ERK2, Jun N-terminal kinase, and p38 MAPK. (hindawi.com)
- Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
- The human muscarinic acetylcholine receptor M 5 , encoded by the CHRM5 gene, is a member of the G protein-coupled receptor superfamily of integral membrane proteins . (wikidoc.org)
- Research suggests that the majority of CB 1 receptors are coupled through G i/o proteins. (wikipedia.org)
- While such systems are valid for evaluating upstream signalling occasions, such as for example receptor conformational adjustments and G proteins activation, these are less robust when you compare downstream signalling outputs as they are apt to be affected by complicated pathway interactions. (healthweblognews.info)
- To see the editorial because of this themed section R406 go to http://dx.doi.org/10.1111/j.1476-5381.2010.00695.x disk huge tumor suppressor (DlgA)/zonula occludens-1 proteins (zo-1)] bind towards the C-terminal tails of focus on proteins like the 2-AR (Hall (2008) PKA had not been involved with receptor phosphorylation. (healthweblognews.info)
- Additionally we are shipping Adenosine A2a Receptor Antibodies (160) and Adenosine A2a Receptor Proteins (7) and many more products for this protein. (antibodies-online.com)
- ERK1/2 and CREB signaling proteins, which are induced by the activation of G-protein coupled receptors (GPCRs), cause plasticity changes and inflammatory responses in the spinal nerves. (ekja.org)
- However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. (aspetjournals.org)
- Mild-to-moderate red wine consumption improves cardiac function in the ischemic myocardium through the protection of endothelial function, the expression of several cardioprotective oxidative stress-inducible proteins, as well as the activation of adenosine receptors and nitrous oxide synthase mechanisms. (blogspot.com)
- While ATP primarily acts as a proinflammatory signal on purinergic P2 receptors, its degradation product adenosine signals through P1 purinergic receptors, mediating both anti- and proinflammatory effects depending on the receptor subtype. (physiology.org)
- The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. (ekja.org)
- In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A 2 adenosine receptor subtype(s) on the cell surface. (physiology.org)
- The serotonin 1A receptor (or 5-HT 1A receptor ) is a subtype of serotonin receptor (5-HT receptor) that binds the neurotransmitter serotonin ( 5-hydroxytryptamine , 5-HT ). (wikidoc.org)
- Furthermore, ado, through the A 2B subtype, induces an increase of Interleukin-8 (IL-8) secretion in a ERK 1/2, p38, and Akt kinase-dependent but not HIF-1α-mediated way. (ahajournals.org)
- The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. (rupress.org)
- We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation. (rupress.org)
- CD73-derived adenosine acts as potent inhibitor of inflammation, and regulatory T cells (Treg) have been shown to express CD73 as a novel marker. (physiology.org)
- In summary, CD73-derived adenosine tonically inhibits active NF-κB in CD4 + T-cells, thereby modulating the release of a broad spectrum of proinflammatory cytokines and chemokines. (physiology.org)
- Adenosine can be formed from AMP either intracellularly by cytosolic 5′-nucleotidase usually involving tissue hypoxia or extracellularly by ecto-5′-nucleotidase (CD73). (physiology.org)
- However, genetic deletion of CD73 in mice is associated with a proinflammatory phenotype and CD73-derived adenosine appears to be quantitatively sufficient to inhibit platelet activation, and leukocyte adhesion to the vascular endothelium in vivo ( 15 ) by acting through the A2aR ( 47 ). (physiology.org)
- Allard D, Allard B, Gaudreau P-O, Chrobak P, Stagg J (2016) CD73-adenosine: a next-generation target in immuno-oncology. (springer.com)
- In addition, it has been recently accepted that adenosine generated from Foxp3 + CD4 + regulatory T cells (Tregs) through CD39/CD73 mediates immune suppression ( 22 , 23 ). (aacrjournals.org)
- Based on the immunomodulatory property of adenosine, we evaluated the role of CD73 in cancer immunity. (aacrjournals.org)
- Hypoxia, high cell turnover, and expression of CD39 and CD73 are important factors in adenosine production. (biomedcentral.com)
- This invention concerns a method of inducing an elevated level of adenosine in an individual by administering to the individual an effective amount of either i) recombinant protein CD73 or ii) a cytokine or another factor being capable of inducing endothelial CD73 expression, or a combination thereof. (patentsencyclopedia.com)
- 2. The method according to claim 1 wherein the elevated level of adenosine is achieved by up-regulating endothelial CD73 expression in the individual by administering to the individual an effective amount of a cytokine. (patentsencyclopedia.com)
- 5. A method for prevention or treatment of a disease or disorder requiring or benefiting from the elevation of the adenosine level in an individual, by administering to said individual an effective amount of amount of either i) recombinant protein CD73 or ii) a cytokine or another factor being capable of inducing endothelial CD73 expression, or a combination thereof. (patentsencyclopedia.com)
- In skeletal muscle, the β-AR-dependent increase of intracellular cAMP is followed by the efflux of cyclic nucleotide via probenecid-sensitive transporters ( Godinho and Costa, 2003 ). (aspetjournals.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)
- A2B adenosine receptor (A2B AR) activation induces Gs-dependent cyclic AMP accumulation. (readbyqxmd.com)
- Receptors on the left of the figure (IP, DP 1 , EP 2 , and EP 4 receptors) predominantly active G s , increase cyclic adenosine monophosphate (cAMP) and are vasodilatory. (comprehensivephysiology.com)
- G sα subsequently activates adenylyl cyclase , increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP). (wikipedia.org)
- Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. (wikidoc.org)
- Recently, uridine adenosine tetraphosphate (Up 4 A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). (hindawi.com)
- NECA acting on adenosine A 2B receptors was much more potent in stimulating ERK1/2 phosphorylation (EC 50 = 19 nM) than cAMP formation (EC 50 = 1.4 μM). (aspetjournals.org)
- Adenosine is a potent vasodilator of small coronary resistance arterioles and does not have any vasoactive effects on the large epicardial arteries. (psychiatryadvisor.com)
- 12 Adenosine delivers potent suppressive effects on virtually all cells of the immune system by interacting with four subtypes of adenosine receptors (ARs), A1, A2A, A2B, and A3. (freedomwares.ca)
- The potent combined cannabinoid agonist WIN 55,212-2 can. (angiogenesis-blog.com)
- Nucleotides and nucleosides act as potent extracellular messengers via the activation of the family of cell-surface receptors termed purinergic receptors. (biomedcentral.com)
- The main mechanism of action of caffeine in the brain seems to be a nonselective competitive blockade of adenosine receptors, in particular adenosine A1 receptors and A2A receptors ( Daly and Fredholm, 1998 ). (jneurosci.org)
- In addition, the stimulation of A2A-mediated responses modulates the control of T cell-mediated colitis in experimental mouse models by suppressing the expression of proinflammatory cytokines in a manner independent of both IL-10 and TGF-β ( 23 ). (rupress.org)
- The effects of clenbuterol/fenoterol (β 2 -AR agonists), forskolin (AC activator), cAMP/8-bromo-cAMP, and adenosine were evaluated on isometric contractility of mouse diaphragm muscle induced by supramaximal direct electrical stimulation (0.1 Hz, 2 ms duration). (aspetjournals.org)
- On murine T lymphocytes the A2aR is highly expressed ( 20 ), and after T-cell receptor (TCR) stimulation, A2aR mRNA levels increase by a factor of ∼10 ( 16 ). (physiology.org)
- Stimulation with the endogenous ligand adenosine resulted in the same pattern of ERK1/2 phosphorylation as NECA. (aspetjournals.org)
- In Val90-A3AR/SERT co-transfections, agonist stimulation elevated SERT activity over the wildtype receptor with delayed 5-HT uptake activity recovery. (biomedcentral.com)
- In contrast, Ile171-A3AR was unable to support agonist stimulation of SERT. (biomedcentral.com)
- In macrophages engulfing apoptotic cells, stimulation of A2ARs suppresses the NO-dependent formation of neutrophil migration factors, such as macrophage inflammatory protein-2, using the adenylate cyclase / protein kinase A pathway. (pubmedcentralcanada.ca)
- Study reveals presence of adenosine A(2A) and A(2B (show ADRA2B ELISA Kits )) receptors as well as a role for them in lacrimal gland secretion, and especially in synergy with purinergic and cholinergic stimulation. (antibodies-online.com)
- Conversely, I GABA generated by "control" GABA A receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn 2+ . (pnas.org)
- We have previously described a characteristic I GABA rundown that occurs during repetitive stimulation of GABA A receptors microtransplanted from the human mesial temporal lobe epilepsy (mTLE) brain into Xenopus oocytes. (pnas.org)
- Under these conditions, it is released into the extracellular space and signals through the stimulation of 4 extracellular G protein-coupled receptors named A 1 , A 2A , A 2B , and A 3 (ARs). (ahajournals.org)
- IFN-γ priming of macrophages selectively prevents the induction of the A2bR in macrophages to mitigate sensitivity to adenosine and to prevent this regulatory transition. (jimmunol.org)
- Thus, we propose a novel mechanism whereby IFN-γ contributes to host defense by desensitizing macrophages to the immunoregulatory effects of adenosine. (jimmunol.org)
- Thus, the generation of adenosine by macrophages is an important mechanism that prevents overactive inflammatory responses. (jimmunol.org)
- The A2b adenosine receptor (A2bAR) is highly abundant in bone marrow macrophages and vascular smooth muscle cells (VSMC). (pnas.org)
- The neuromodulator adenosine regulates immune activation and neuronal survival through specific G-protein-coupled receptors expressed on macrophages and neurons, including the A1 adenosine receptor (A1AR). (jneurosci.org)
- Although, adenosine activating its receptors (A 1 , A 2A , A 2B and A 3 ) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. (elsevier.es)
- In the present study, using wild type and adenosine A 2A receptor (A2AR) null mice, we investigated whether A2ARs, known to mediate anti-inflammatory signals in macrophages, participate in the apoptotic cell-mediated immunosuppression. (pubmedcentralcanada.ca)
- We found that macrophages engulfing apoptotic cells release adenosine in sufficient amount to trigger A2ARs, and simultaneously increase the expression of A2ARs, possibly via activation of activation of liver X receptor and peroxisome proliferators activated receptor δ. (pubmedcentralcanada.ca)
- Altogether our data indicate that adenosine is one of the soluble mediators released by macrophages that mediate engulfment-dependent apoptotic cell suppression of inflammation. (pubmedcentralcanada.ca)
- For example, preincubation of macrophages with apoptotic cells strongly suppresses the inflammatory response induced via Toll-like receptor 4 by lipopolysaccharide, a component of the cell wall of Gram-negative bacteria ( 4 - 6 ). (pubmedcentralcanada.ca)
- Therefore, because of the link between ado, inflammation, and angiogenesis and the increasing evidence that these factors play a role in atherogenesis, we thought to investigate HIF-1α, VEGF, IL-8, and FC formation by ado receptors in human macrophages and in an in vitro model of human FCs. (ahajournals.org)
- [email protected]#To explore the action mechanism of acupoint selection along meridians to improve adenosine receptor in myocardial ischemia (MI) rats by comparing the effects of acupoint selection along meridians, acupoint selection at other meridians and non-acupoint on expression of adenosine receptor. (bvsalud.org)
- To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
- Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (physiology.org)
- Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (physiology.org)
- The adenosine analog 5′- N -ethylcarboxamidoadenosine (NECA), known to act on all subtypes, had no effect on untransfected CHO cells, but did cause a substantial time- and dose-dependent phosphorylation in CHO cells transfected with each of the receptors. (aspetjournals.org)
- For all receptors the half-maximal ERK1/2 phosphorylation was observed at 19-115 nM NECA. (aspetjournals.org)
- We explored Gi, Gq/11 and Gs coupling in 1321 N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously expressing human A2B AR, using NECA or nonnucleoside BAY60-6583 as agonist, selective Gi, Gs and Gq/11 blockers, and CRISPR/Cas9-based Gq- and Gs-null HEK293 cells. (readbyqxmd.com)
- Concentration-response curves (CRCs) of adenosine receptor (AR) agonists, NECA (nonspecific), CCPA (A1 specific), CGS-216870 (A2A specific), BAY 60-6583 (A2B specific), and Cl-IB-MECA (A3 specific) for mesenteric arteries (MAs) from 4 AR knockout (KO) mice (A1, A2A, A2B, and A3) and their wild type (WT) were constructed. (saladgaffe.tk)
- This inhibition grows more pronounced when considered with the effect of activated CB1 receptors to limit calcium entry into the cell, which does not occur through cAMP but by a direct G-protein-mediated inhibition. (wikipedia.org)
- Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
- Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. (aspetjournals.org)
- We identify A 2B as the primary receptor limiting mast cell degranulation, whereas the combined activity of A 2A and A 2B is required for the inhibition of cytokine synthesis. (aspetjournals.org)
- Upon treating the cells or rats with LPS, activation of the A2AAR was the most efficient in mediating AR agonist- or CBD-induced TNF-α inhibition. (freedomwares.ca)
- These results suggest that the activated A2AAR in the retinal microglial cells plays a major role in anti-inflammation in the retina, and that CBD anti-inflammatory effects are linked to adenosine uptake inhibition. (freedomwares.ca)
- In general, synaptic receptor subtypes contain a γ 2 subunit, which is critical for maintaining receptors at synaptic sites, have low affinity for GABA, and mediate fast inhibitory transmission, the so-called phasic (transient) inhibition. (pnas.org)
- In contrast, extrasynaptic receptor subtypes containing α 4 , α 5 , or α 6 subunits and/or a δ instead of a γ subunit, exhibit high affinity for GABA and mediate tonic (persistent) inhibition ( 1 - 6 ). (pnas.org)
- Tonic currents are caused by GABA that escapes presynaptic uptake and produces slow neuronal inhibition through a persistent activation of extrasynaptic GABA A receptors. (pnas.org)
- Impairement of GABA A receptor-mediated inhibition increases neuronal excitability and plays a critical role during epileptogenesis ( 7 ). (pnas.org)
- Using in vivo microdialysis in freely moving rats, we demonstrate that systemic administration of behaviorally relevant doses of caffeine can preferentially increase extracellular levels of dopamine and glutamate in the shell of the NAc. (jneurosci.org)
- In the striatum, adenosine plays an important role as a modulator of both dopamine and glutamate neurotransmission. (jneurosci.org)
- Although the latter mechanism is very well established, evidence for a dopamine-releasing effect of behaviorally relevant doses of caffeine in brain regions that may mediate its psychostimulant actions has not yet been obtained. (jneurosci.org)
- Only a previous study by Morgan and Vestal (1989) , using in vivo voltammetry, indicated that low doses of caffeine increase dopamine release in the rat caudate putamen. (jneurosci.org)
- ASP5854 also significantly restored the striatal dopamine content reduced by 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment in mice at doses higher than 0.1 mg/kg. (curehunter.com)
- 2001 ) and potentiated rotational behavior produced by L -DOPA or dopamine agonists in 6-OHDA-lesioned rats (Fenu et al. (biomedsearch.com)
- 1998 ) and produced synergistic effect when added to dopamine agonists (Kanda et al. (biomedsearch.com)
- All set up antipsychotic medicines antagonize dopamine D2 receptors, and their scientific efficacy correlates straight using their occupancy of D2 receptors (Seeman et al. (sprentland.com)
- Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). (wikipedia.org)
- The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors. (wikipedia.org)
- Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. (wikipedia.org)
- The existence of multiple types of receptors for dopamine was first proposed in 1976. (wikipedia.org)
- There are at least five subtypes of dopamine receptors, D 1 , D 2 , D 3 , D 4 , and D 5 . (wikipedia.org)
- The D 1 and D 5 receptors are members of the D 1 -like family of dopamine receptors, whereas the D 2 , D 3 and D 4 receptors are members of the D 2 -like family . (wikipedia.org)
- There is also some evidence that suggests the existence of possible D 6 and D 7 dopamine receptors, but such receptors have not been conclusively identified. (wikipedia.org)
- D 3 is encoded by the Dopamine receptor D 3 gene ( DRD3 ). (wikipedia.org)
- Maximum expression of dopamine D 3 receptors is noted in the islands of Calleja and nucleus accumbens . (wikipedia.org)
- D 4 is encoded by the Dopamine receptor D 4 gene ( DRD4 ). (wikipedia.org)
- Dopamine receptors have been shown to heterodimerize with a number of other G protein-coupled receptors . (wikipedia.org)
- Dopamine receptor D 1 and Dopamine receptor D 5 are G s coupled receptors that stimulate adenylyl cyclase to produce cAMP , increasing intracellular calcium among other cAMP mediated processes. (wikipedia.org)
- Dopamine receptor activation of Ca 2+ /calmodulin-dependent protein kinase II can be cAMP dependent or independent. (wikipedia.org)
- 5-HT 1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex , striatum , and hippocampus , and may be useful for improving the symptoms of schizophrenia and Parkinson's disease . (wikidoc.org)
- Up 4 A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. (hindawi.com)
- This study explored the role of endogenously formed adenosine in modulating NF-κB activity and cytokine/chemokine release from murine Treg and effector T cells (Teff) including key enzymes/purinergic receptors of extracellular ATP catabolism. (physiology.org)
- Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. (readbyqxmd.com)
- Three recent reports have examined the relationship between the level of extracellular ATP, the mechanisms underlying purinergic receptors participating in the infection mechanism of HIV-1 in the cell. (biomedcentral.com)
- Seminal, important genetic data indicate that adenosine, which is operative via the A2A adenosine receptor, plays critical, nonredundant, autonomous, and autochthonous roles in inhibiting effector functions of activated T cells ( 19 , 20 ). (rupress.org)
- increase muscle contraction force via activation of stimulatory G protein (G s )-coupled receptors (GPCRs), which in turn activates adenylyl cyclases (ACs). (aspetjournals.org)
- Although adenosine activates multiple receptor subtypes (A1, A2a, A2b, and A3 receptors), the adenylyl cyclase stimulatory A2a adenosine receptors (A2aARs) are regarded mainly as cardioprotective receptors ( 1 ). (pnas.org)
- Upon subcutaneous administration, abaloparatide acts similar to PTHrP and targets, binds to and activates parathyroid hormone 1 (PTH1) receptor (PTH1R), a G protein-coupled receptor (GPCR) expressed in osteoblasts and bone stromal cells. (cancer.gov)
- The amino acid L- glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors . (wikidoc.org)
- In this regard, the level of nucleoside adenosine is increased in individuals with obesity. (elsevier.es)
- Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. (wikidoc.org)
- A 1 receptors are expressed in the renal microcirculation 1 where they induce renal vasoconstriction, mediate tubuloglomerular feedback, 2 - 4 augment renal vasoconstriction induced by angiotensin II 5 , 6 and norepinephrine, 7 , 8 and are essential for a full renovascular response to renal sympathetic nerve activation. (highwire.org)
- 7 , 8 A 1 receptors also mediate vasoconstriction in the aorta 9 , 10 and mesenteric arteries, 11 , 12 and A 1 receptors in the nucleus tractus solitarii increase sympathetic outflow. (highwire.org)
- 14 - 18 A 2A receptors mediate vasodilation in many vascular beds including the kidneys, 19 - 22 heart, 23 mesentery, 24 , 25 skeletal muscle, 26 , 27 and aorta. (highwire.org)
- 34 - 37 A 2B receptors mediate vasodilation, for example in the kidneys, 38 , 39 heart, 23 , 40 , 41 mesentery, 11 and aorta. (highwire.org)
- To provide insights into the relationship between the specific GABA A receptor isoform composition and the functional impairement of GABAergic inhibitory systems resulting in seizures, we have begun to explore the GABA A receptor populations that mediate the I GABA rundown. (pnas.org)
- These data show that adenosine and A 1 ARs potently regulate mammalian heart rates via multiple effector systems at very early stages of prenatal development. (elsevier.com)
- 2-5 A 1 receptors (A 1 R) and A 3 receptors (A 3 R) are expressed in cardiomyocytes, and a substantial body of evidence indicates that adenosine can protect the heart during and after an ischemic insult. (ahajournals.org)
- Adenosine A2A receptor contributes to ischemic brain damage in newborn piglet. (antibodies-online.com)
- Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. (bvsalud.org)
- Adenosine (Ado) is a proangiogenic purine nucleoside released from ischemic and hypoxic tissues. (ahajournals.org)
- ASP5854 ameliorated A(2A) agonist 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680)- and haloperidol-induced catalepsy in mice, with the minimum effective doses of 0.32 and 0.1 mg/kg, respectively, and it also improved haloperidol-induced catalepsy in rats at doses higher than 0.1 mg/kg. (curehunter.com)
- To examine the functional significance of this receptor expression, we applied a femoral artery injury model to A2bAR knockout (KO) mice and showed that the A2bAR prevents vascular lesion formation in an injury model that resembles human restenosis after angioplasty. (pnas.org)
- Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits. (abcam.com)
- Outcomes Vilazodone Serves as an Agonist at 5-HT1A Autoreceptors in Mice 5-HT1A agonists stimulate an instant hypothermic response when injected systemically. (healthweblognews.info)
- B) Mice injected with vilazodone [VIL] 1, 3, and 10mg/kg demonstrated dose-dependent lowers in body's temperature (n = 5C8 mice/group). (healthweblognews.info)
- Hedrich J, Angamo EA, Conrad A, Lutz B, Luhmann HJ (2020) Cell type specific impact of cannabinoid receptor signaling in somatosensory barrel map formation in mice. (unimedizin-mainz.de)
- Mice with a knocked out mGluR5 show a lack of cocaine self-administration regardless of dose. (wikidoc.org)
- Uppal H, Toma D, Saini S, Ren S, Jones T, Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. (labome.org)
- Several studies have also suggested that the beneficial effects of adenosine occur through the effects of the A2AR and A2BR ( 7 , 22 , 27 , 43 ). (physiology.org)
- However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. (frontiersin.org)
- Metabotropic glutamate receptor 5 is a G protein-coupled receptor that in humans is encoded by the GRM5 gene . (wikidoc.org)
- This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux via inward rectifier K+ channels, subsequently inhibiting Ca2+ current. (wikipedia.org)
- β 2 -Adrenoceptor (β 2 -AR) agonists increase skeletal muscle contractile force via activation of G s protein/adenylyl cyclases (AC) and increased generation of cAMP. (aspetjournals.org)
- Indirect evidence suggests that the adenylyl cyclase stimulatory A2b adenosine receptors (A2bARs) also affect vascular function ( 4 - 6 ). (pnas.org)
- First, a localized signal is generated by a G protein-coupled receptor paired to one or more of the nine different transmembrane adenylyl cyclase isoforms that generate the cAMP signal in the cytosol. (aspetjournals.org)
- The D2 class of receptors produce the opposite effect, as they are G αi coupled receptors, and block the activity of adenylyl cyclase. (wikipedia.org)
- The final aim is to consider the role of adenosinergic ectoenzymes and ADO receptors as novel therapeutic targets for selected diseases. (hindawi.com)
- Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal, such as a human, wherein the activity, i.e.9 over-activity, of adenosine A2B receptors is implicated in one or more symptoms of the pathology and antagonism (i.e.9 blocking) of their activity is desired to ameliorate said symptoms. (allindianpatents.com)
- Kumar V, Sharma A (2009) Adenosine: an endogenous modulator of innate immune system with therapeutic potential. (springer.com)
- Iannone R, Miele L, Maiolino P et al (2014) Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model. (springer.com)
- A2A AR activation on BBB (show ALMS1 ELISA Kits ) endothelial cells offers a therapeutic window that can be fine-tuned for drug delivery to the brain and has potential as a CNS drug-delivery technology. (antibodies-online.com)
- In this review, we will examine the rationale for therapeutic blockade of this pathway, provide an overview of preclinical data, briefly describe ongoing clinical work, and assess potential future applications targeting the adenosine pathway in cancer immunotherapy. (biomedcentral.com)
- Our findings point to the rundown of GABA A receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABA A receptor activity may represent a useful therapeutic approach to the disease. (pnas.org)
- In unilateral 6-hydroxydopamine-lesioned rats, ASP5854 significantly potentiated l-dihydroxyphenylalanine (L-DOPA)-induced rotational behavior at doses higher than 0.032 mg/kg. (curehunter.com)
- To explore the impact of electroacupuncture (EA) on the protein expression of adenosine receptors in the heart of the rats with myocardial ischemia (MI). (readbyqxmd.com)
- Vascular dysfunction and fibrosis in stroke-prone spontaneously hypertensive rats: The aldosterone-mineralocorticoid receptor-Nox1 axis. (abcam.com)
- 25 MTX-glu represent long lived derivatives, which in rats may be detected in the skin for as long as two weeks after a single dose of the drug. (bmj.com)
- Adenosine receptors influence blood pressure and survival in salt-sensitive rats, and the impact of deleting adenosine receptors on blood pressure and survival depends on salt diet and sex. (highwire.org)
- The synthesis and distribution of the kinin B1 and B2 receptors are modified in the hippocampus of rats submitted to pilocarpine model of epilepsy. (mdc-berlin.de)
- Additionally, we found that GABA A receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. (pnas.org)
- In this study we therefore compared the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) via the four known human adenosine receptors A 1 , A 2A , A 2B , and A 3 , stably transfected into Chinese hamster ovary (CHO) cells. (aspetjournals.org)
- The maximal phosphorylation was highest in A 1 and A 3 receptor-transfected cells, intermediate in A 2A and low in A 2B receptor-expressing CHO cells. (aspetjournals.org)
- Concentrations of adenosine that occur physiologically caused an increased phosphorylation after 5 min in CHO cells transfected with any one of the four adenosine receptors. (aspetjournals.org)
- In exploration of the mechanisms, we found that PTX stimulated IL-10 production through the phosphorylation of STAT3, and A2A receptor participated in this regulation. (pubmedcentralcanada.ca)
- 1996). "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. (wikidoc.org)
- The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG) and other signaling pathways leading to enhanced SERT surface expression and catalytic activity. (biomedcentral.com)
- For example, AVPR1B causes secretion of ACTH from the anterior pituitary cells in a dose-dependent relationship by activating protein kinase C via the Gq/11 protein. (worldheritage.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)
- As hypoxia induces HIF-1α stabilization and adenosine (ado) accumulation, we investigated whether this nucleoside regulates HIF-1α in FCs. (ahajournals.org)
- Neuronal Adenosine A2A Receptors Are Critical Mediators of Neurodegeneration Triggered by Convulsions. (nih.gov)
- The late descending phase of the β 2 -AR agonist inotropic effect was mimicked by either cAMP or adenosine and abolished by preincubation of diaphragm with pertussis toxin (PTX) (G i signaling inhibitor) or the organic anion transporter inhibitor probenecid, indicating a delayed coupling of β 2 -AR to G i protein which depends on cAMP efflux. (aspetjournals.org)
- An orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. (cancer.gov)
- In keeping with LY2140023 this likelihood, a thorough 6 month research aimed at producing a HIV-1 stress resistant to the cyclin-dependent kinase inhibitor, LY2140023 roscovitine, demonstrated unsuccessful . (angiogenesis-blog.com)
- 12. The method according to claim 5 wherein an adenosine deaminase inhibitor which prevents the decomposition of adenosine, is administered. (patentsencyclopedia.com)
- This contraction was also inhibited by ethacrynic acid, by inhibitors of Na+, K+-ATPase (ouabain), Ca2+- ATPase (thapsigargin), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, by a non-selective phosphodiesterase inhibitor (papaverine), and by adenosine A2 (metrifudil), and cannabinoid receptor (CP-55940) agonists. (omicsonline.org)
- The inverse agonist MK-9470 makes it possible to produce in vivo images of the distribution of CB1 receptors in the human brain with positron emission tomography. (wikipedia.org)
- In addition to the main neurotransmitter-receptor signal, several signaling pathways coordinate the pre- and postsynaptic cells and associated glia in the tripartite synapses in accordance with functional demands. (frontiersin.org)
- Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. (drugbank.ca)
- 6,7 Liao et al 8 demonstrated that the adenosine analogue 2-chloroadenosine (CADO) also attenuated pressure overload-induced LV hypertrophy through activation of the A 1 R. Similar to A 1 R, the A 3 R are Gi protein-coupled receptors that have been shown to activate similar downstream signaling pathways. (ahajournals.org)
- Here, we investigated the role of the A2B adenosine receptor (A2BAR) and its associated signaling pathways in governing the proliferation and viability of breast cancer cell line derived CSCs. (readbyqxmd.com)
- Cdc20.24 Altogether these Mec1-dependent pathways cooperate to arrest cells in metaphase using a characteristic large-budded cell phenotype a brief mitotic spindle and high degrees of Pds1/securin and M-CDK activity. (bioinbrief.com)
- Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5 . (wikipedia.org)
- Background The positive transcription elongation factor, P-TEFb, made up of cyclin dependent kinase 9 (Cdk9) and cyclin T1, T2 or K regulates the productive elongation phase of RNA polymerase II (Pol II) dependent transcription of cellular and integrated viral genes. (angiogenesis-blog.com)
- Genes coding for tyrosine kinase receptors (TKR) involved with oncogenesis such as for example are inconsistently turned on (2C15% of situations), most via amplifications often. (buyresearchchemicalss.net)
- Some of the atypical antipsychotics like lurasidone and aripiprazole are also partial agonists at the 5-HT 1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs). (wikidoc.org)
- As mentioned above, some of the atypical antipsychotics are 5-HT 1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy. (wikidoc.org)
- It has been recognized that theophylline and its closely related analogue caffeine block endogenous adenosine acting as a local modulator of adenosine receptors in the brain and other organs at therapeutically useful doses. (allindianpatents.com)
- In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased adenylate cyclase activity and acid production. (physiology.org)
- Whether adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated. (physiology.org)
- Increased levels of peroxynitrite, tyrosine nitrations of FSH receptor (FSHR) and apoptosis were obviously detectable with decreased FSHR protein expressions in granulosa cells of the poor ovarian responders. (aging-us.com)
- En general, el posacondicionamiento reduce el daño inducido por la reperfusión, disminuyendo el daño oxidativo y atenuando la respuesta inflamatoria local durante la reperfusión, así también disminuye el tamaño del infarto, disminuyendo el proceso de apoptosis, la activación neutrofílica y la disfunción endotelial. (scielo.org.mx)
- Hypoxic postconditioning attenuates apoptosis via inactivation of adenosine A2a receptor through NDRG3 - Raf (show RAF1 ELISA Kits )- ERK (show EPHB2 ELISA Kits ) pathway. (antibodies-online.com)
- After treatment, the TTC staining was used to detect myocardial infarction, the Tunel method was used to detect cardiomyocyte apoptosis, and the immunohistochemistry was used to detect the expression of adenosine receptors A1, A2a and A2b. (bvsalud.org)
- In addition, the rapid clinical remission and the short term effect on the acute phase reactants, as seen with low dose MTX administration in most patients with RA, as well as the fast flare of disease after drug discontinuation, suggest that the mechanism of action of low dose MTX might be more anti-inflammatory than antiproliferative (immunosuppressive). (bmj.com)