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 A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.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.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.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Receptors, Adenosine A2: A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 18.104.22.168.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 Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Piperidines: A family of hexahydropyridines.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.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.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.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.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.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.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.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.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.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.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.Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.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.Biphenyl CompoundsRadioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.TetrazolesAdrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Benzazepines: Compounds with BENZENE fused to AZEPINES.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.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.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Sulfonamides: A group of compounds that contain the structure SO2NH2.5'-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 22.214.171.124.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)Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).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.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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Purinergic P2X Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.Azepines: Seven membered heterocyclic rings containing a NITROGEN atom.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.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)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)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.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.Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.Receptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.Receptor, Endothelin B: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.TriazolesNeurons: 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.Behavior, Animal: The observable response an animal makes to any situation.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.PiperazinesDevazepide: A derivative of benzodiazepine that acts on the cholecystokinin A (CCKA) receptor to antagonize CCK-8's (SINCALIDE) physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding.Receptors, Cholecystokinin: Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.PyrrolidinesReceptors, Vasopressin: Specific molecular sites or proteins on or in cells to which VASOPRESSINS bind or interact in order to modify the function of the cells. Two types of vasopressin receptor exist, the V1 receptor in the vascular smooth muscle and the V2 receptor in the kidneys. The V1 receptor can be subdivided into V1a and V1b (formerly V3) receptors.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Quinoxalines2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.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.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.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.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Injections, Intraventricular: Injections into the cerebral ventricles.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Receptors, Neurokinin-2: A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid 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.Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.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.QuinuclidinesAdrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.BenzodiazepinonesKinetics: The rate dynamics in chemical or physical systems.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.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Receptors, Histamine H3: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Adenine NucleotidesMineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.QuinolinesDogs: 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)Pyrilamine: A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.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.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.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.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.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.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.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.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.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).Mice, Inbred C57BLPhenylpropionatesAntihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.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.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Oligopeptides: Peptides composed of between two and twelve amino acids.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)Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.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.Receptors, Calcitonin Gene-Related Peptide: Cell surface proteins that bind CALCITONIN GENE-RELATED PEPTIDE with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the CENTRAL NERVOUS SYSTEM and the periphery. They are formed via the heterodimerization of the CALCITONIN RECEPTOR-LIKE PROTEIN and RECEPTOR ACTIVITY-MODIFYING PROTEIN 1.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.Isoindoles: Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.Receptors, Corticotropin-Releasing Hormone: Cell surface proteins that bind corticotropin-releasing hormone with high affinity and trigger intracellular changes which influence the behavior of cells. The corticotropin releasing-hormone receptors on anterior pituitary cells mediate the stimulation of corticotropin release by hypothalamic corticotropin releasing factor. The physiological consequence of activating corticotropin-releasing hormone receptors on central neurons is not well understood.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.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Receptors, Tachykinin: Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.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.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)Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.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.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.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.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.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.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.Proglumide: A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers.Dioxanes: 1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)Receptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)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.Memantine: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Receptors, Histamine H2: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.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.Purinergic P2Y Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.
Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. (1/50)1. Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A1, A2A and A3 adenosine receptors in this phenomenon. 2. The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity. 3. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nm), completely prevented the protective effect of preconditioning. The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phe nol (ZM 241385, 100 nm) did not modify the magnitude of fepsp recovery compared to control slices. The selective A3 adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nm) significantly improved the recovery of fepsps after 7 min of ischemia. 4. Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A1 receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A2A receptors are not involved in this phenomenon, whereas A3 receptor activation is harmful to ischemic preconditioning. (+info)
Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. (2/50)Recent studies demonstrated that resveratrol, a grape-derived polyphenolic phytoalexin, provides pharmacological preconditioning (PC) of the heart through a NO-dependent mechanism. Because adenosine receptors play a role in PC, we examined whether they play any role in resveratrol PC. Rats were randomly assigned to groups perfused for 15 min with 1) Krebs-Henseleit bicarbonate buffer (KHB) only; 2) KHB containing 10 microM resveratrol; 3) 10 microM resveratrol + 1 microM 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A(1) receptor blocker); 4) 10 microM resveratrol + 1 microM 8-(3-chlorostyryl)caffeine (CSC; adenosine A(2a) receptor blocker); 5) 10 microM resveratrol + 1 microM 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5- dicarboxylate (MRS-1191; adenosine A(3) receptor blocker); or 6) 10 microM resveratrol + 3 microM 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride [LY-294002, phosphatidylinositol (PI)3-kinase inhibitor], and groups perfused with adenosine receptor blockers alone. Hearts were then subjected to 30-min ischemia followed by 2-h reperfusion. The results demonstrated significant cardioprotection with resveratrol evidenced by improved ventricular recovery and reduced infarct size and cardiomyocyte apoptosis. CPT and MRS 1191, but not CSC, abrogated the cardioprotective abilities of resveratrol, suggesting a role of adenosine A(1) and A(3) receptors in resveratrol PC. Resveratrol induced expression of Bcl-2 and caused its phosphorylation along with phosphorylation of cAMP response element-binding protein (CREB), Akt, and Bad. CPT blocked phosphorylation of Akt and Bad without affecting CREB, whereas MRS 1191 blocked phosphorylation of all compounds, including CREB. LY-294002 partially blocked the cardioprotective abilities of resveratrol. The results indicate that resveratrol preconditions the heart through activation of adenosine A(1) and A(3) receptors, the former transmitting a survival signal through PI3-kinase-Akt-Bcl-2 signaling pathway and the latter protecting the heart through a CREB-dependent Bcl-2 pathway in addition to an Akt-Bcl-2 pathway. (+info)
Activation of A3 adenosine receptors attenuates lung injury after in vivo reperfusion. (3/50)BACKGROUND: A3 adenosine receptor (AR) activation worsens or protects against renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the current study were to examine in an in vivo model the effect of A3AR activation on IR lung injury and investigate the mechanism by which it exerts its effect. METHODS: The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A3 receptor agonist IB-MECA (300 microg/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. RESULTS: IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52 +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. CONCLUSIONS: In the feline lung, the A3AR agonist IB-MECA confers a powerful protection against IR lung injury. This effect is mediated by a nitric oxide synthase-independent pathway and involves opening of adenosine triphosphate-sensitive potassium channels. Therefore, selective activation of A3AR may be an effective means of protecting the reperfused lung. (+info)
A3 adenosine receptor activation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase 1/2 phosphorylation in A375 human melanoma cells. (4/50)Adenosine exerts its effects through four subtypes of G-protein-coupled receptors: A(1), A(2A), A(2B), and A(3). Stimulation of the human A(3) receptor has been suggested to influence cell death and proliferation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt and the Raf/mitogen-activated protein kinase (MAPK/ERK) kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways have central roles in the regulation of cell survival and proliferation. Due to their importance, the cross-talk between these two pathways has been investigated. Here, we show that the A(3) adenosine receptor agonist Cl-IB-MECA stimulates PI3K-dependent phosphorylation of Akt leading to the reduction of basal levels of ERK1/2 phosphorylation, which in turn inhibits cell proliferation. The response to Cl-IB-MECA was not blocked by A(1), A(2A), or A(2B) receptor antagonists, although it was abolished by A(3) receptor antagonists. Furthermore, the response to Cl-IB-MECA was generated at the cell surface, since the inhibition of A(3) receptor expression, by using small interfering RNA, abolished agonist effects. Using A375 cells, we show that A(3) adenosine receptor stimulation results in PI3K-dependent phosphorylation of Akt, leading to the reduction of basal levels of ERK1/2 phosphorylation, which in turn inhibits cell proliferation. (+info)
Resveratrol-mediated activation of cAMP response element-binding protein through adenosine A3 receptor by Akt-dependent and -independent pathways. (5/50)A recent study documented a role of adenosine A(3)-Akt-cAMP response element-binding protein (CREB) survival signaling in resveratrol preconditioning of the heart. In this study, we demonstrate that resveratrol-mediated CREB activation can also occur through an Akt-independent pathway. Isolated rat hearts were perfused for 15 min with Krebs-Henseleit bicarbonate (KHB) buffer containing resveratrol in the absence or presence of adenosine A(3) receptor blocker MRS-1191 [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5 -dicar-boxylate], phosphatidylinositol 3 (PI3)-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], mitogen-activated extracellular signal-regulated protein kinase inhibitor PD098059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one], or a combination of LY294002 and PD098059. All hearts were subsequently subjected to 30-min ischemia followed by 2-h reperfusion. Cardioprotection was examined by determining infarct size, cardiomyocyte apoptosis, and ventricular recovery. Resveratrol phosphorylated both Akt and CREB that was blocked by MRS-1191, which also abolished cardioprotective abilities of resveratrol. LY294002 completely inhibited Akt phosphorylation but partially blocked the phosphorylation of CREB. Inhibition of PI3-kinase also partially blocked resveratrol's ability to precondition the heart. PD098059 partially blocked the phosphorylation of CREB and resveratrol-mediated cardioprotection. Preperfusing the hearts with LY294002 and PD098059 together completely abolished the phosphorylation of CREB, simultaneously inhibiting resveratrol-mediated cardioprotection. The results indicate that resveratrol preconditions the hearts through adenosine A(3) receptor signaling that triggers the phosphorylation of CREB through both Akt-dependent and -independent pathways, leading to cardioprotection. (+info)
Phosphatidylinositol 3-kinase and ERK1/2 are not involved in adenosine A1, A2A or A3 receptor-mediated preconditioning in rat ventricle strips. (6/50)Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (PKB; also known as Akt) are important antiapoptotic signalling pathways which have recently been implicated in cardioprotection. However, at present the involvement of ERK1/2 and PI3-kinase/PKB in adenosine receptor-mediated cardioprotection is poorly understood. In this study we used isolated rat right ventricular strips, contracted by electrical-field stimulation, in order to investigate the role of ERK1/2 and PI3-kinase/PKB in adenosine receptor-induced cardioprotection. Ventricle strips were pretreated for 2 min with the agonists adenosine (non-selective), CPA (A1 selective), CGS 21680 (A2A selective) and Cl-IB-MECA (A3 selective) before 30 min hypoxia followed by 30 min reoxygenation. Each agonist significantly improved posthypoxic percentage contraction recovery compared to control strips. Similarly hypoxic preconditioning (10 min hypoxia followed by 20 min reoxygenation) significantly improved posthypoxic percentage contraction recovery compared to non-preconditioned strips. The selective adenosine receptor antagonists DPCPX (A1), ZM 241385 (A2A) and MRS 1220 (A3) attenuated cardioprotection induced by CPA, CGS 21680 and Cl-IB-MECA, respectively. Pre-incubation (30 min) of ventricle strips with the MEK1 inhibitor PD 98059 (50 microM) or the PI3-kinase inhibitor wortmannin (100 nM) significantly reduced posthypoxic percentage contraction recovery induced by hypoxic preconditioning. In contrast, PD 98059 and wortmannin had no significant effect on cardioprotection induced by CPA, Cl-IB-MECA or CGS 21680. Overall these data indicate that although selective A1, A2A and A3 adenosine receptor agonists induce preconditioning in rat right ventricular strips the effects are independent of ERK1/2- and PI3-kinase-dependent pathways. In contrast ERK1/2 and PI3-kinase-dependent pathways do appear to be involved in early hypoxic preconditioning. (+info)
"Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists. (7/50)The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N(6)-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K(i) value of 0.66 microM. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N(6)-cyclohexyladenine (12), 2-(phenylamino)-N(6)-cycloheptyladenine (19), and 2-phenylamino-N(6)-endo-norbornyladenine (21) as potent A(3) AR ligands with K(i) values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (>200-fold) was 2-(phenyloxy)-N(6)-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy > or = amino > thio. Selected derivatives, including reversine (K(B) value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N(6) position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation. (+info)
The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure. (8/50)PURPOSE: Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. METHODS: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. RESULTS: Adenosine triggered A3AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 +/- 11 nM, p < 0.01) and by another A3AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 +/- 0.8 mmHg at 25-microM droplet concentration (n = 10, p < 0.005). CONCLUSIONS: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist. (+info)
So this weekend I bid goodbye to another Sac-Con. Le sigh, if only it was more than a one day con... Wait, what did you say? Its GONNA BE!?? Thats frikkin right! From now on, Sac Con (henceforth to be referred to as SUPER Sac-Con) is gonna be a weekend long event! Boy howdy! I guess the reality of WonderCon never returning to the bay is finally sinking in, and a lot of the smaller cons are revving up their game, trying to be the next big contender. Just a week prior to Fanime was a lil show called Big Wow Con, which if youre native to the bay area, you might remember as formerly being referred to as Super Con ...
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The European Food Safety Authority (EFSA) carried out an exposure assessment of Brilliant Black BN (E 151), taking into account new information on its use as a food additive in foods. In 2010, the EFSA Panel on Food Additives and Nutrient Sources added to .... ...
The European Food Safety Authority (EFSA) carried out an exposure assessment of Brilliant Black BN (E 151), taking into account new information on its use as a food additive in foods. In 2010, the EFSA Panel on Food Additives and Nutrient Sources added to .... ...
The enzyme is most active with L-methionine. It participates in the L-methionine salvage pathway from S-methyl-5-thioadenosine, a by-product of polyamine biosynthesis. T
Catalyzes the reversible phosphorylation of S-methyl-5-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.
SWISS-MODEL Repository entry for C4YQD9 (MTAP_CANAW), S-methyl-5-thioadenosine phosphorylase. Candida albicans (strain WO-1) (Yeast)
By: Chris Niles Armstead Maupin meets Carl Hiaasen in a brilliant black comedy that traces the paths of disparate characters floating through New York, about to collide in a treacherous story that will make you think twice about ever answering a classified ad. ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
Heres the really interesting part. People like you guys, who have been keeping up with this the whole way through, youll already know that its a superhero story. However, people are getting BAAU Down 12 and seeing Brilliant Black Starres for the first time will be totally blind sided. The super hero aspect of the story is more like a twist at the end of the chapter as opposed to a running theme, so Im sure it will catch readers off guard. Im also relatively certain that Brilliant Black Starres is gonna be this huge, runaway major success, so being the first appearance of the characters will turn BAAU Down 12 into a huge collectors item on par with Action Comics #1. Im totally serious about this. So when you stop by this Fanime, dont just get one, get a few! Positively guaranteed to skyrocket in value! this could be your childs college fund! Not even kidding ...
This is a pretty good hit rate. Generally virtual screening campaigns are lucky to have a hit rate of a few percent. Curiously, the authors also found a similarly high hit rate during a past VS campaign against the well-known β2 adrenergic receptor. What could be responsible for this high hit rate against GPCRs? The reasons are interesting. One reason could be that GPCRs are very well adapted to bind small molecules in compact pockets, enclosing them and forming many kinds of productive interactions. But more intriguingly, as the authors have noted earlier, there is "biogenic bias" in favor of certain target-specific chemotypes in commercial libraries that are screened, both during VS as well as HTS. This in turn reflects the biases of medicinal chemists in picking and synthesizing certain kinds of chemotypes based on the importance of drug targets and past successes in hitting these targets. GPCRs clearly are enormously important, and GPCR-friendly ligand chemotypes thus constitute a large ...
WASPADAI 50 JENIS ZAT PEWARNA DAN ZAT ADITIF DALAM MAKANAN ANAK ANDA COLOUR Artificial colours Allura red AC 129 Amaranth 123 Azorubine, carmoisine 122 Brilliant Black BN 151 Brilliant Blue FCF133 Brown HT, chocolate brown 155 Erythrosine 127 Green S, food green, acid brilliant green 142 Indigotine, indigo carmine 132 Ponceau, brilliant scarlet 4R…
He has done it again. Alexander Von Meilenwald has put out another brilliant Black metal opus. I am now fully convinced that this man is a musical genius. I know reviewers need to maintain a sense of objectivity, but we also need to recognize brilliant music whenever it slaps us in the face and have the balls to spread the word. And well, this is us fucking wreckingball ...
MRS-4200 Satin Hot Rod Black is a 2K acrylic urethane coating developed for restoration work, coating frames, engine compartments, exterior panels and other surfaces that a black satin finish is required. This product mixes 4:1 with either MRS-4205 Regular activator or MRS-4210 Slow Activator. MRS-4200 Satin Hot Rod Black has excellent adhesion and chemical resistance. Formulated for long term durability. Available in quarts and gallons. ...
Growing evidence suggests functional interaction between CFTR and P2YR. P2Y2R can regulate CFTR activity in different systems (Paradiso et al., 2001; Marcet et al., 2003). Here, we extend these findings by showing that CFTR modulates the P2Y1R signaling pathway. We report that CHO cells express, in addition to P2Y2R (Marcet et al., 2003), the P2Y1R subtype, which does not regulate CFTR activity in CHO-BQ1 cells. Moreover, we show that, in CHO cells, the expression of the recombinant CFTR (CHO-BQ1), but not the expression of the vector alone (CHO-KNUT), causes an apparent switch in the G-protein-coupling of P2Y1R from a Gq/11- to Gi/o-type. This change in G-protein selectivity was specific of P2Y1R since P2Y2R G-protein-coupling remained unaffected by CFTR.. Our findings that the P2Y1R antagonist MRS2179 and the P2Y1R knockdown antisense experiments abolished the ADP-induced Ca2+ response strongly suggest that putative hamster homologous of human P2Y12- or P2Y13-Gi protein-coupled receptors are ...
Home » S-adenosylhomocysteine. s-adenosylhomocysteine (Science: chemical) 5-s-(3-amino-3-carboxypropyl)-5-thioadenosine. Formed from s-adenosylmethionine after transmethylation reactions. Chemical name: L-Homocysteine, S-(5-deoxyadenosin-5-yl)- ...
... is known to act as an antagonist of the adenosine A3 receptor. Reversine is a potent inhibitor of the mitotic kinase ...
... is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM ... Müller CE (2003). "Medicinal chemistry of adenosine A3 receptor ligands". Current Topics in Medicinal Chemistry. 3 (4): 445-62 ... a novel high-affinity antagonist radioligand for human A(3) adenosine receptors". Bioorg Med Chem Lett. 12 (3): 501-3. doi: ... "Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia". Naunyn-Schmiedeberg's Archives of ...
... is a drug which acts as a potent and selective antagonist for the adenosine A3 receptor, with sub-nanomolar affinity ( ... a new potent and selective adenosine A3 receptor antagonist". European Journal of Pharmacology. 444 (3): 133-41. doi:10.1016/ ... Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and ... A3 Ki=0.2nM) and high selectivity over the other three adenosine receptor subtypes. Simple xanthine derivatives such as ...
Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive ... The role of A3 receptor is less defined in this field. Studies have shown that it plays a role in the downregulation of ... The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as endogenous ... Br J Pharmacol 170(6):1167-1176 "Entrez Gene: ADORA2A adenosine A2A receptor". Jacobson KA, Gao ZG (2006). "Adenosine receptors ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry. 46 (7 ... Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ... The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it. This ...
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ... adenosine receptor". Mol. Pharmacol. 63 (5): 1021-31. doi:10.1124/mol.63.5.1021. PMID 12695530. "Adenosine Receptors: A3". ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ...
2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". J. Comp ... Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S (December 2005). "A2B adenosine receptor antagonists: recent ... The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human ... "The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". J. Biol. Chem ...
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...
... is an antagonist at all four adenosine receptor subtypes (A1, A2A, A2B, and A3), although with varying potencies. The ... this is a receptor complex with 1 adenosine A1 receptor and 1 dopamine D1 receptor) and the A2A-D2 receptor heterotetramer ( ... this is a receptor complex with 2 adenosine A2A receptors and 2 dopamine D2 receptors). The A2A-D2 receptor heterotetramer has ... a receptor complex composed of 1 adenosine A1 receptor and 1 adenosine A2A receptor) in the axon terminal of glutamate neurons ...
Caffeine acts as an antagonist of adenosine A1 and A2A receptors. Adenosine is a normal neuromodulator that activates adenosine ... There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this ... Caffeine also has an excitatory effect on mesocortical cholinergic neurons by acting as an antagonist on adenosine receptors ...
... such as nicotinic ACh receptors -at micromolar concentrations- or adenosine A3. The exact effects of methoctramine still remain ... Watson, N.; Barnes, P.J.; Maclagan, J. (1992). "Actions of methoctramine, a muscarinic M2 receptor antagonist, on muscarinic ... Gallamine triethiodide M2 receptor Muscarinic receptor Acetylcholine Jakubik, Jan; Zimcik, Pavel; Randakova, Alena; Fuksova, ... Hence, the presence of the antagonist methoctramine provokes an increase of the heart rate. In marked contrast of the above, ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular ... N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (5): 1612-6. PMID ... Entrez Gene: ADORA3 adenosine A3 receptor".. *^ Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry 46 (7 ... 3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: a study on the importance of modifications at the ... 1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): ...
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... This is being contended and it is now considered a relative contraindication (however, selective adenosine antagonists are ... Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Extracellular ... The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ...
"Anti-platelet therapy: ADP receptor antagonists". British Journal of Clinical Pharmacology. 72 (4): 647-657. doi:10.1111/j.1365 ... 157 (1): 148.e1-148.e5. doi:10.1016/j.ahj.2008.09.017. Drepper, Michael D; Spahr, Laurent; Frossard, Jean Louis (2012-05-14). " ... P2Y12 receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y12 receptor that leads to ... Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute ...
The antagonist reagent is used together with TRAP-test, and allows assessment of a positive control. Prostaglandin E1 (PGE1) is ... Thrombin receptor activating peptide-6 (TRAP-6) activates platelets through the thrombin receptor protease activated receptor-1 ... Adenosine diphosphate (ADP) is a platelet agonist. When it is added to saline-diluted whole blood in the test cuvette, it ... The GPIIb/IIIa antagonist blocks the binding of fibrinogen to the GPIIb/IIIa receptors, preventing the formation of platelet- ...
... leading to an accumulation of adenosine. On the other hand, the adenosine-receptor antagonist caffeine reverses the anti- ... On the other hand, nanomolar concentrations of adenosine activate A1 and A3 receptors, resulting in neutrophilic chemotaxis ... In the airways of patients with asthma, the expression of adenosine receptors is upregulated. Adenosine receptors affect ... the expression of adenosine receptors on the neutrophil, and the affinity of these receptors for adenosine. Micromolar ...
Björklund O, Shang M, Tonazzini I, Daré E, Fredholm BB (2008). "Adenosine A1 and A3 receptors protect astrocytes from hypoxic ... H2-receptor antagonists, like cimetidine (Tagamet), inhibit the signaling pathway that leads to activation of the ATPase. This ... eCollection 2015 Gessi S, Merighi S, Stefanelli A, Fazzi D, Varani K, Borea PA (2013). "A(1) and A(3) adenosine receptors ... Memory has been associated with astrocytes and the alpha3 subunit of adenosine receptor found in hydrogen/Sodium-potassium ...
Antagonists may be used primarily in hypertension, anxiety disorder, and panic attacks. The α2 receptor couples to the Gi/o ... 81 (1): 211.e1-7. doi:10.1016/j.urology.2012.09.011. PMID 23200975. Fitzpatrick D, Purves D, Augustine G (2004). "Table 20:2". ... "Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway ... a Gq coupled receptor) and α2 (a Gi coupled receptor). Phenylephrine is a selective agonist of the α receptor. β receptors have ...
These Receptor antagonist, which block EP3 from responding to PGE2 or other agonists of this receptor, include Sulprostone, DG- ... Prostaglandin E1 (PGE1), which has one less double bond than PGE2, has the same binding affinity and potency for EP3 as PGE2. ... and pathways that inhibit adenyl cyclase which thereby lowers cellular levels of cyclic adenosine monophosphate (cAMP) to ... Eicosanoid receptor Prostaglandin E2 receptor 1 (EP1) Prostaglandin E2 receptor 2 (EP2) Prostaglandin E2 receptor 4 (EP4) ...
Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... Leukotriene-A4 hydrolase), or are the cellular receptors responsible for mediating the cellular responses to the down-stream ... may serve as a mobile lid over ALOX5's substrate-binding site An Adenosine triphosphate (ATP) binding site; ATP is crucial for ... as well as of LTC4 and LTD4 receptor antagonists have proven inferior to corticosteroids as single drug therapy for persistent ...
J. W. Black; A. F. Crowther; R. G. Shanks; A. C. Dornhorst (1964). "A new adrenergic beta-receptor antagonist". The Lancet. 283 ... A. Vulpian (1856). "Note sur quelques réactions propres à la substance des capsules surrénales". Comptes Rendus de l'Académie ... In addition the vesicles contained adenosine triphosphate (ATP), with a molar noradrenaline:ATP ratio in sympathetic nerve ... he called alpha adrenotropic receptor (now α-adrenoceptor or α-adrenergic receptor), while the receptor with the second rank ...
Endogenous CB1 antagonist and CB2 agonist) Rimonabant Taranabant Lipoxin A4 - endogenous, PAM ZCZ-011 - PAM Pregnenolone - ... Through its primary action as a Gi coupled receptor, CB1 inhibits production of cyclic adenosine monophosphate (cAMP), ... Discovery and development of Cannabinoid Receptor 1 Antagonists Cannabinoid receptor Cannabinoid receptor type 2 (CB2) GRCh38: ... As a consequence, CB1 receptor antagonists can reduce drug seeking behavior in some addicts. The CB1 receptor is expressed by a ...
Cannabinoid receptor agonists reduce gut motility in IBS patients. Application of CB2-specific antagonists has found that these ... CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP). Although the ... 11: e3. doi:10.1017/S1462399409000957. PMC 2768535 . PMID 19152719. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, ... Unlike the CB1 receptor, in the brain, CB2 receptors are found primarily on microglia. The CB2 receptor is expressed in some ...
"Entrez Gene: TACR3 tachykinin receptor 3".. *^ Quartara L, Altamura M (Aug 2006). "Tachykinin receptors antagonists: from ... "Tachykinin Receptors: NK3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... NK3 receptor antagonists are being investigated as treatments for various indications. ... tachykinin receptor activity. • G-protein coupled receptor activity. • signal transducer activity. • protein binding. ...
transmembrane signaling receptor activity. • Wnt-activated receptor activity. • G-protein coupled receptor activity. ... "Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action". Proc. Natl. Acad. Sci. U.S.A. 94 ... "Frizzled Receptors: FZD5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ... To this aim, the identification of antigens and receptors involved in GBM/immune cell interactions and of GBM immune escape ... To this aim, the identification of antigens and receptors involved in GBM/immune cell interactions and of GBM immune escape ... Regional Differences in Adaptation of CNS Mu Opioid Receptors to Chronic Opioid Agonist Administration. Current ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ... These molecules belong to a family of vasopressin receptor antagonists, V2 in particular, that regulate optional renal water re ... These molecules belong to a family of vasopressin receptor antagonists, V2 in particular, that regulate optional renal water re ... Pharmacophoric Models and 3D QSAR Studies of the Adenosine Receptor Ligands. Current Topics in Medicinal Chemistry ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ... Vilaprisan, a New Selective Progesterone Receptor Modulator in Uterine Fibroid Pharmacotherapy-Will it Really be a Breakthrough ...
Reversine is a potent human A3 adenosine receptor antagonist with Ki of 0.66 μM, ... is a new adenosine A1 receptor agonist. R10848. Ki16198. Ki16198 is the methyl ester of Ki16425, which is a LPA antagonist and ... Bosentan is an endothelin (ET) receptor antagonist for ET-A and ET-B with Ki of ... Ambrisentan is a highly selective antagonist of the endothelin-1 type A receptor ...
Med: ADENOSINE. Indication: SVT. Dose: 6-12mg FAST PUSH. Comes in 6mg/2mL vial. 1-2 vials/dose.. Med: AMIODARONE. Indication: ... 1 amp raises pH 0.1 à Goal pH 7.2ish. • 8.4% NaHCO3 ≅ 6% HTS. • 2 amps bicarb = 100cc 6% = 200cc 3% (can substitute for HTS in ... Indication: Bradycardia (Muscarinic antagonist). Dose: 0.5 mg. Vial comes in 1mg/1mL (2 doses per syringe).. Repeat q 1-3 ... Low doses: , 2mcg/kg/min -dopamine receptors (vasodilate). Mid dose: 5-10mcg/kg/min - β1 (contractility/HR). High dose: , 10 ...
The cardiac pharmacology of tiotidine (LCL 125, 211): a new histamine H2-receptor antagonist. J P Trzeciakowski and R Levi ... Binding of adenosine to the crude plasma membrane fraction isolated from dog coronary and carotid arteries. P Dutta and S J ... Peripheral vasodilator effects of prostaglandins: comparison of 6-keto-prostaglandin E1 with prostacyclin and escape from ... The cardiac pharmacology of tiotidine (LCL 125, 211): a new histamine H2-receptor antagonist. J P Trzeciakowski and R Levi ...
A3 receptor/Adenosine A3 receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL256] [GtoPdb: 21] [UniProtKB: P0DMS8] ... Antagonist activity at AT1 receptor in rat aorta F 8 pKd 10 nM Kd Eur. J. Med. Chem. (2008) 43: 1808-1812 [PMID:18158200] ... A3 receptor/Adenosine A3 receptor in Human [ChEMBL: CHEMBL256] [GtoPdb: 21] [UniProtKB: P0DMS8] ... AT1 receptor in Human [GtoPdb: 34] [UniProtKB: P30556] *AT1 receptor/Type-1A angiotensin II receptor in Rat [ChEMBL: CHEMBL329 ...
... as well as A2-adenosine receptor agonists and antagonists (see column 2, lines 61 to 66) and as it is specifically said in ... Prenez quelques minutes de votre temps pour répondre à cette enquête sur notre site Internet et gagnez lun des dix sacs de ... the development of new adenosine receptor drugs (either agonist or antagonist) has been impeded by the multiplicity of effects ... As it is said in the application in suit that the claimed compounds provide a selective A1-adenosine receptor antagonistic ...
3H]N-methylscopolamine binding to muscarinic receptors in intact adult rat brain cell aggregates. Lee, J. H. & El-Fakahany, E. ...
Jan 06, progesterone receptor antagonist that affects your doctor service. Loteprednol is also commonly referred to treat ... hopital foch à suresnes, clinique de la muette dans le 16eme ou hopital maternité foch - suresnes - avis???? hopital beaujon ( ... Trihexyphenidyl is quite enjoyable level, special dry mouth ethambutol therapy of adenosine uptake and quit smoking. This ... Hq generic viagra is a herb extract that is ↑ h 2-receptor antagonist depending on dna. Tranexamic acid and irritable and holds ...
cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila). 0.014. ... T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3. 0.014. ... adenosine deaminase, RNA-specific. 0.029. Stat6. signal transducer and activator of transcription 6. 0.029. ... BCL2-antagonist/killer 1. 0.015. Efnb2. ephrin B2. 0.014. Ciita. class II transactivator. 0.014. ...
Adenosine A1 Receptors *Adenosine A2A Receptors *Adenosine A2B Receptors *Adenosine A3 Receptors ... Interestingly, the use of a HIF-2 antagonist, recently developed  decreases systemic iron accumulation in hepcidin- ... HIF-1 in addition has been shown to modify transferrin receptor 1 (TfR1) and heme oxygenase 1 (HO-1) manifestation [17,18], but ...
... and possibly D1 receptors. Heat shock protein cognate 70-4 and an E3 ubiquitin ligase, CHIP, mediate plastid-destined precursor ... Additive vasodilator therapy with calcium-channel antagonists is under investigation. To investigate the relationship between ... important physiological platelet inhibitors is endothelium-derived prostacyclin which stimulates the platelet cyclic adenosine ... Immunocytochemistry, receptor binding assays and in situ hybridizations have demonstrated VIP abundance in the nervous system, ...
The AMPA receptor GluA2 (GluR2) tetramer was the first and currently only glutamate receptor ion channel to be crystallized. ... AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. ... is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central ... Adenosine Receptor. Adiponectin Receptor. Adrenergic Receptor. Angiotensin Receptor. Bombesin Receptor. Bradykinin Receptor. ...
HX 531 is a potent antagonist of retinoid X receptors (IC50 = 18 nM).. ... Adenosine Receptor. *Dopamine Receptor. *Endothelin Receptor. *Neurokinin Receptor. * Endocrinology & Hormones *GPR. *Estrogen ... Fenretinide is shown to exhibit binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death. ... Bexarotene is a retinoid specifically selective for retinoid X receptors, used as an oral antineoplastic agent in the treatment ...
MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 ... Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti- ... We have previously shown that activation of the cyclic adenosine monophosphate (cAMP)/PKA pathway in ALL cells promotes ... 9-11 gain-of-function mutations in the E3 ligase HDM2 that promotes degradation of p53 are frequent.12 Still, it is reasonable ...
Endothelin Receptors. *LPA Receptor. *Prostanoid Receptors. *Adenosine Receptors. *Cannabinoid Receptors. *Neurotensin ... MDM2 antagonist nutlin-3 is a potent inducer of apoptosis.. Add to Wishlist ... E3 Ligase Ligand-Linker Conjugate. *E3 Ligase Ligands. *PROTAC Degrader. *PROTAC Linker ...
Ebastine is a second-generation H1 receptor antagonist that is indicated mainly for allergic rhinitis and chronic idiopathic ... It does not penetrate the blood-brain barrier to a significant amount and thus combines an effective block of the H1 receptor ... 5-HT Receptor * 19 GPCR & G Protein * Adenosine Receptor * Adrenergic Receptor * cAMP ... Ebastine is a second-generation H1 receptor antagonist that is indicated mainly for allergic rhinitis and chronic idiopathic ...
Rat AIP(Aryl Hydrocarbon Receptor Interacting Protein) ELISA Kit. *Rat ARNT2(Aryl Hydrocarbon Receptor Nuclear Translocator 2) ... Rat BAK1(BCL2 Antagonist/Killer 1) ELISA Kit. *Rat BAX(BCL-2 Associated X Protein) ELISA Kit ... LXA4(Lipoxin A4) ELISA Kit. *6-keto-PGF1a(6-keto-prostaglandin F1a) ELISA Kit ... cAMP(Cyclic adenosine monophosphate) ELISA Kit. *TXA2(Thromboxane A2) ELISA Kit. *Cr(Creatinine) ELISA Kit ...
Rat AIP(Aryl Hydrocarbon Receptor Interacting Protein) ELISA Kit. *Rat ARNT2(Aryl Hydrocarbon Receptor Nuclear Translocator 2) ... Rat BAK1(BCL2 Antagonist/Killer 1) ELISA Kit. *Rat BAX(BCL-2 Associated X Protein) ELISA Kit ... LXA4(Lipoxin A4) ELISA Kit. *6-keto-PGF1a(6-keto-prostaglandin F1a) ELISA Kit ... cAMP(Cyclic adenosine monophosphate) ELISA Kit. *TXA2(Thromboxane A2) ELISA Kit. *Cr(Creatinine) ELISA Kit ...
MY 336-a is a beta-adrenergic receptor antagonist produced by Streptomyces gabonae. ... 5-HT Receptor * 19 GPCR & G Protein * Adenosine Receptor * Adrenergic Receptor * cAMP ...
Moreover, the transcription of OATP1B3-1B7 can be modulated by farnesoid X receptor (FXR) agonists and antagonists. FXR is a ... The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 ( ... Such adverse events are dependent on many transporters, particularly those in the solute carrier and adenosine triphosphate- ... Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination ...
LigandsAgonists and antagonistsSubtypesMedicinal ChemistryPharmacologyLigandSubtypeDerivativesAffinityInhibitsExtracellularCyclicPharmacologicalInhibitionEffects of adenosineInhibitorSelectivityBindsNonselective adenosineA3ARCaffeineProteinsGeneSelective antagonistsAdenylyl cyclaseNucleosideInhibitoryAllostericTypes of adenosine receptorsEndogenous adenosineInhibitAgonist CP-532,903StimulationDopamineSignal TransductionAntagonismProteinDemonstrate that adenosinePhysiological functionsDiphosphateHumanActivation by adenosineTriphosphateTargetsRole of adenosineHistamineInflammationConcentrationsPurinergicADORA3MechanismIntracellular
- When appropriately modified, they show selectivity toward A1 or A3 receptors, which results in a variety of therapeutic potentialities of these ligands. (nih.gov)
- Application of datasets by using CODESSA software led to QSAR equations based on three and four descriptors for the adenosine A1 and A3 receptor ligands, respectively. (nih.gov)
- Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
- A number of selective A3 ligands are available. (wikipedia.org)
- Selective" Class C G Protein-Coupled Receptor Modulators Are Neutral or Biased mGlu 5 Allosteric Ligands. (nih.gov)
- However the development of more highly selective A2A ligands has led towards other applications, with the most significant focus of research currently being the potential therapeutic role for A2A antagonists in the treatment of Parkinson's disease. (wikipedia.org)
- Also disclosed are conjugates comprising a dendrimer and one or more ligands, which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. (nih.gov)
- Research into selective A2B ligands has lagged somewhat behind the development of ligands for the other three adenosine receptor subtypes, but a number of A2B-selective compounds have now been developed, and research into their potential therapeutic applications is ongoing. (wikipedia.org)
- Novel ligands (small molecules) for these receptors are developed using classical synthetic approaches and also by semirational methods based on molecular modeling and template design. (nih.gov)
- Recent accomplishments include the design and synthesis of the highly potent and selective A3 adenosine receptor agonists and antagonists, using a combination of library screening and optimization of known adenosine receptor ligands. (nih.gov)
- These cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands. (biomedsearch.com)
- The A 3 receptor is more and more being well-known for its organic roles through the physique, and lots of A 3 receptor ligands have confirmed important in elucidating peripheral and principal pathologies. (stainlessqa.com)
- The CB1 receptor can also be modulated by allosterically synthetic ligands in a positive and negative manner. (wikipedia.org)
- The C-terminus of CB2 receptors appears to play a critical role in the regulation of ligand-induced receptor desensitization and downregulation following repeated agonist application, perhaps causing the receptor to become less responsive to particular ligands. (wikipedia.org)
- Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase. (wikipedia.org)
- Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. (wikipedia.org)
- Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. (ovid.com)
- Our overall goals are to design, chemically synthesize, and characterize pharmacologically new agonists and antagonists for the four subtypes of adenosine receptors (ARs) and eight subtypes of P2Y receptors and to explore their potential for treating human disease conditions. (nih.gov)
- This application relates to uses of A.sub.2a adenosine receptor agonists and antagonists to modulate T-cell mediated tolerance to antigenic stimuli. (patents.com)
- This review emphesizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. (eurekaselect.com)
- PSB-10 is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM), with high selectivity over the other three adenosine receptor subtypes (ki values at human A1, A2A and A2B receptors are 4.1, 3.3 and 30 µM). (wikipedia.org)
- The adenosine receptors are classified into the subtypes of A1, A2 (2A and 2B), and A3. (patent-de.com)
- These G protein-coupled receptors transduce activation or inhibition of adenylate cyclase and phospholipase C. Reasonably selective antagonists are available for some adenosine receptor subtypes. (cdc.gov)
- The gene encodes a protein which is one of several receptor subtypes for adenosine. (wikipedia.org)
- However, Y1/Y5 receptor BiFC dimers, compared with the constituent subtypes, were characterized by reduced potency and efficacy of Y5-selective peptide agonists, the inactivity of Y1-selective antagonists, and a change from surmountable to nonsurmountable antagonism for three unrelated Y5 antagonists. (aspetjournals.org)
- KF-26777 is a drug which acts as a potent and selective antagonist for the adenosine A3 receptor, with sub-nanomolar affinity (A3 Ki=0.2nM) and high selectivity over the other three adenosine receptor subtypes. (wikipedia.org)
- Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
- Four adenosine receptor subtypes of the family of G protein-coupled receptors, designated A1, A2A, A2B and A3 are currently known. (biomedsearch.com)
- In this study all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). (biomedsearch.com)
- In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. (biomedsearch.com)
- Adenosine is an endogenous and ubiquitous nucleoside that exerts many biological functions through interaction with 4 distinct subtypes of G protein-coupled receptors divided into A1, A2A, A2B, and A3. (unife.it)
- There are two main groups of adrenergic receptors, α and β, with several subtypes. (wikipedia.org)
- α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor). (wikipedia.org)
- β receptors have the subtypes β1, β2 and β3. (wikipedia.org)
- New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism. (nih.gov)
- For two Y1 receptor heterodimer combinations (with the Y4 receptor or β 2-adrenoceptor), agonist and antagonist pharmacology was explained by independent actions on the respective orthosteric binding sites. (aspetjournals.org)
- Thus, allosteric interactions between Y1 and Y5 receptors modify the pharmacology of the heterodimer, with implications for potential antiobesity agents that target centrally coexpressed Y1 and Y5 receptors to suppress appetite. (aspetjournals.org)
- A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR. (eurekaselect.com)
- Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: the state of the art. (eurekaselect.com)
- I am a medicinal chemist with interests in the structure and pharmacology of receptors and in developing drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
- Thus, in marked contrast to the β-adrenoceptors, the A1-receptor conforms to the long-held principle of pharmacology that antagonist affinity measurements are constant regardless of the response being measured and the competing agonist used to stimulate that response. (aspetjournals.org)
- A3 Adenosine Receptors from Cell Biology to Pharmacology and by John R. Fozard (auth. (stainlessqa.com)
- This booklet "A3 Adenosine Receptors from telephone Biology to Pharmacology and Therapeutics " files the current country of information of the adenosine A3 receptor. (stainlessqa.com)
- A3 Adenosine Receptors from mobile Biology to Pharmacology and Therapeutics" is an up to the moment and scientifically very good resource of knowledge, beautiful to simple and medical scientists alike. (stainlessqa.com)
- Pharmacology of Histamine Receptors provides a precis of the pharmacology of histamine receptors. (stainlessqa.com)
- In this session the latest research in the field of receptor pharmacology and signal transduction will be presented. (figondmd.nl)
- In 1954, he was able to incorporate his findings in a textbook, Drill's Pharmacology in Medicine, and thereby promulgate the role played by α and β receptor sites in the adrenaline/noradrenaline cellular mechanism. (wikipedia.org)
- A 2012 study published in the European Journal of Pharmacology concluded that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A2A receptor. (wikipedia.org)
- The CellAura fluorescent adenosine A 3 antagonist [XAC] ligand was shown to antagonize the activity of the adenosine receptor agonist, NECA, in three separate recombinant CHO cell lines expressing the human A 1 , A 2A or A 3 receptor and a cyclic AMP-responsive secreted placental alkaline phosphatase (SPAP) reporter gene. (hellobio.com)
- The adenosine receptors (or P1 receptors ) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand . (wikipedia.org)
- Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor. (nih.gov)
- A live cell NanoBRET binding assay allows the study of ligand-binding kinetics to the adenosine A 3 receptor. (nih.gov)
- Development of novel fluorescent histamine H 1 -receptor antagonists to study ligand-binding kinetics in living cells. (nih.gov)
- Despite its structure, uridine triphosphate (UTP) is a potent ligand at several P2Y-receptors. (cdc.gov)
- The crystallographic structure of the adenosine A2A receptor reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin). (wikipedia.org)
- Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. (nus.edu.sg)
- Receptors are computer-modeled by homology to GPCRs of known structure, and the models for ligand recognition are tested and refined using site-directed mutagenesis of the receptor proteins. (nih.gov)
- The antagonist affinity for a given receptor is traditionally considered to be constant, reflecting the chemical nature of the specific ligand-receptor interaction. (aspetjournals.org)
- The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG). (wikipedia.org)
- Based on computer modeling, ligand interactions with CB2 receptor residues S3.31 and F5.46 appears to determine differences between CB1 and CB2 receptor selectivity. (wikipedia.org)
- Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors. (wikipedia.org)
- The receptors that allow this influx and outflow are the ionotropic receptors, which are ligand-gated ion channels that bind specific neurotransmitters, released from the synaptic vesicles of the presynaptic terminal, to trigger the opening of the channels, which serve as conduits for cations that, in turn, initiate action potential across the post synaptic terminals of normally functioning neurons. (wikipedia.org)
- The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that interacts with (binds) epinephrine, a hormone and neurotransmitter (ligand synonym, adrenaline) whose signaling, via a downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation. (wikipedia.org)
- Beta-2 adrenergic receptors have also been found to couple with Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. (wikipedia.org)
- The nociceptin receptor is a member of the opioid subfamily of G protein-coupled receptors whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). (wikipedia.org)
- Likewise, classical opioid receptors possess little affinity towards NOP's endogenous ligand nociceptin, which is structurally related to dynorphin A. In 1994, Mollereau et al. (wikipedia.org)
- Simple xanthine derivatives such as caffeine and DPCPX have generally low affinity for the A3 subtype and must be extended by expanding the ring system and adding an aromatic group to give high A3 affinity and selectivity. (wikipedia.org)
- The affinity towards adenosine A3 subtype was measured against the radioligand PSB-11. (wikipedia.org)
- Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A3 receptor subtype. (semanticscholar.org)
- The receptors for adenine nucleotides, such as adenosine triphosphate (ATP), now encompass seven distinct P2X class receptors (P2X1 through P2X7) and ten P2Y subfamily receptors: P2Y1 through P2Y11 (the former P2Y7-receptor is no longer included as a subtype). (cdc.gov)
- In the past most of the anti-inflammatory effects of this nucleoside were thought to be due to the activation of the A2A subtype, however more recently, the involvement of the A3 subtype has been also considered relevant for the outcome of inflammation. (unife.it)
- Finally, in lymphocytes, activation of A3 receptor subtype would result in a reduction of the accession of killer T cells to tumor cells by exerting an immunosuppressive effect and suggesting a role for antagonists of this receptor as anti-tumoral drugs. (unife.it)
- Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A 1 and A 2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. (wikipedia.org)
- A Structure-Activity Relationship Study of Bitopic N 6 -Substituted Adenosine Derivatives as Biased Adenosine A 1 Receptor Agonists. (nih.gov)
- N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes. (semanticscholar.org)
- Epub 2007 Aug 1.New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. (nus.edu.sg)
- Perreira et al (2005) "Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists. (scbt.com)
- The N6-benzyl substituted derivatives of adenosine-5'-N-methyluronamide (MECA) turned out to be the most potent agonists. (biomedsearch.com)
- Cytokinin ribosides (N6-substituted adenosine derivatives) are nucleoside analogues that have shown anticancer activity both in vitro and in vivo in mammals [ 3 - 11 ]. (alliedacademies.org)
- Derivatives of adenosine are widely found in nature and play an important role in biochemical processes, such as energy transfer-as adenosine triphosphate (ATP) and adenosine diphosphate (ADP)-as well as in signal transduction as cyclic adenosine monophosphate (cAMP). (wikipedia.org)
- In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. (biomedsearch.com)
- The notion of xanthine-insensitivity of the A3 receptor should be dropped at least for the human receptor as xanthines with submicromolar affinity were found. (biomedsearch.com)
- Therefore, we studied the influence of different agonists on antagonist affinity measurements for G i - and G s -coupled conformations of the adenosine A1-receptor in Chinese hamster ovary cells stably expressing the human adenosine A1-receptor and a cAMP-response element (CRE)-secreted placental alkaline phosphatase reporter gene. (aspetjournals.org)
- However, the antagonist affinity values measured at the G i -coupled and G s -coupled conformations of the receptor were the same in both functional responses and whole-cell binding. (aspetjournals.org)
- Consequently, antagonist affinity measurements at a given species homolog of a particular receptor should remain constant regardless of the method used to measure it, provided that the chemical composition of the receptor has not changed. (aspetjournals.org)
- Changes in antagonist affinity measurements have been noted at all human β-adrenoceptors. (aspetjournals.org)
- Antagonist affinity estimates at many GPCRs may indeed depend upon the nature of the agonist used. (aspetjournals.org)
- Biochemical literature distinguishes 5 different types of muscarinic receptors, each of one having a different affinity to methoctramine: Please note that, the lower the affinity constants are, the more affinity exists. (wikipedia.org)
- Activation also induces a conformational change in the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor, giving it high affinity for fibrinogen. (wikipedia.org)
- Binding of TRAP-6 to PAR-1 causes a conformational change in the GPIIb/IIIa receptors on platelets, giving them high affinity for fibrinogen. (wikipedia.org)
- it is one of four identified EP receptors, the others being EP1, EP2, and EP4, all of which bind with and mediate cellular responses to PGE2 and also, but generally with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). (wikipedia.org)
- Prostaglandin E1 (PGE1), which has one less double bond than PGE2, has the same binding affinity and potency for EP3 as PGE2. (wikipedia.org)
- The cytoplasmic-open E1 and luminal-open E2 states have high affinity for H+ and K+. (wikipedia.org)
- Cannabidiol has very low affinity for the cannabinoid CB1 and CB2 receptors but acts as an indirect antagonist of these receptors. (wikipedia.org)
- Although NOP shares high sequence identity (~60%) with the 'classical' opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), it possesses little or no affinity for opioid peptides or morphine-like compounds. (wikipedia.org)
- The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. (drugbank.ca)
- It is known that the interaction with the adenosine A3 receptor inhibits several activities of these cells including the release of TNF-alpha and other potent inflammatory cytokines such as IL-6 and IL-8 and increases the production of IL-10 with anti-inflammatory activity. (unife.it)
- Here, we demonstrate that adenosine, at concentrations that are typically present in the extracellular fluid of solid tumors, exerts a profound inhibitory effect on the induction of mouse cytotoxic T cells, without substantially affecting T-cell viability. (nih.gov)
- Adenine nucleosides and nucleotides have multiple effects as extracellular mediators in every organ system and initiate or modulate cellular responses via cell surface receptors. (cdc.gov)
- Extracellular adenosine gathers in response to cellular stress and breakdown through interactions with hypoxia induced HIF-1α. (wikipedia.org)
- Abundant extracellular adenosine can then bind to the A2A receptor resulting in a Gs-protein coupled response, resulting in the accumulation of intracellular cAMP, which functions primarily through protein kinase A to upregulate inhibitory cytokines such as transforming growth factor-beta (TGF-β) and inhibitory receptors (i.e. (wikipedia.org)
- My current focus is on receptors for purines, encompassing both adenosine receptors and P2 receptors, which are activated by ATP, UTP and other extracellular nucleotides. (nih.gov)
- Recently, the involvement of extracellular loops of GPCRs have been implicated in the receptor binding of small molecules. (nih.gov)
- The study shows effects of the nonselective adenosine A(1)/A(2A) receptor antagonist caffeine and the selective A(2A) receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A(2A) receptor density in the rat striatum. (biomedsearch.com)
- Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. (biomedsearch.com)
- Caffeine (10 and 20 mg/kg i.p.) and KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA, adenosine, glutamate, and hydroxyl radical production. (biomedsearch.com)
- The A3 receptor activation also led to an increase in extracellular levels of MMP9 in the supernatants of glioblastoma cells as evaluated by ELISA and gelatine zymography assays. (unife.it)
- Purinergic signalling (or signaling: see American and British English differences) is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. (wikipedia.org)
- The purinergic signalling system consists of transporters, enzymes and receptors responsible for the synthesis, release, action, and extracellular inactivation of (primarily) ATP and its extracellular breakdown product adenosine. (wikipedia.org)
- There are two types of NTs: Concentrative nucleoside transporters (CNTs): Na+-dependent symporters Equilibrative nucleoside transporters (ENTs): Na+-independent passive transporters The extracellular concentration of adenosine can be regulated by NTs, possibly in the form of a feedback loop connecting receptor signaling with transporter function. (wikipedia.org)
- Extracellular AMP is hydrolyzed to adenosine by ecto-5'-nucleotidase (eN) as well as by APs. (wikipedia.org)
- The CB1 receptor shares the structure characteristic of all G-protein-coupled receptors, possessing seven transmembrane domains connected by three extracellular and three intracellular loops, an extracellular N-terminal tail, and an intracellular C-terminal tail. (wikipedia.org)
- To determine the apparent KD for CellAura fluorescent adenosine A 3 antagonist [XAC], cells were treated with varying concentrations of NECA alone, or in the presence of 1µM CellAura fluorescent adenosine A 3 antagonist [XAC], and the cyclic AMP-induced expression of SPAP measured. (hellobio.com)
- Characterisation of endogenous A 2A and A 2B receptor-mediated cyclic AMP responses in HEK 293 cells using the GloSensor™ biosensor: Evidence for an allosteric mechanism of action for the A 2B -selective antagonist PSB 603. (nih.gov)
- pathways that activate phospholipase C to convert cellular phospholipids to diacylglycerol which promotes the activation of certain isoforms of protein kinase C, pathways that elevated cellular cytosolic Ca2+ which thereby regulate Ca2+-sensitive cell signaling molecules, and pathways that inhibit adenyl cyclase which thereby lowers cellular levels of cyclic adenosine monophosphate (cAMP) to reduce the activity of cAMP-dependent signaling molecules. (wikipedia.org)
- and to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine monophosphate (cAMP), an intracellular signal that serves broadly to inhibit platelet activation. (wikipedia.org)
- This receptor-channel complex is coupled to the Gs G protein, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A, and counterbalancing phosphatase PP2A. (wikipedia.org)
- NOP coupling to Gαi or Gαo subunits leads to an inhibition of adenylyl cyclase (AC) causing an intracellular decrease in cyclic adenosine monophosphate(cAMP) levels, an important second messenger for many signal transduction pathways. (wikipedia.org)
- Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function (by pharmacological inhibition or in P2Y(2)(-/-) mice). (nih.gov)
- Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists. (nih.gov)
- Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy In: ed Protein Reviews. (eurekaselect.com)
- We are interested in correlating structure of receptors and small molecular drugs with pharmacological properties. (nih.gov)
- Substances developed as potent and selective agents acting through adenosine and P2 receptors have proven useful as pharmacological probes and have potential for treating diseases of the central nervous system, immune system, and cardiovascular system. (nih.gov)
- The pharmacological probes designed in our section have been used to demonstrate the connection between purine receptors and apoptosis (programmed cell death). (nih.gov)
- They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT1 and Cys-LT2. (eurekaselect.com)
- Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. (biomedsearch.com)
- The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. (biomedsearch.com)
- Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. (aspetjournals.org)
- CB2 was cloned in 1993 by a research group from Cambridge looking for a second cannabinoid receptor that could explain the pharmacological properties of tetrahydrocannabinol. (wikipedia.org)
- As these "classical" opioid receptors were identified 30 years earlier in the mid-1960s, the physiological and pharmacological characterization of NOP as well as therapeutic development targeting this receptor remain decades behind. (wikipedia.org)
- Is Combined Angiotensin-converting Enzyme Inhibition and Angiotensin Receptor Blockade Associated with Increased Risk of Cardiovascular Death in Hemodialysis Patients? (eurekaselect.com)
- Mice treated with A2AR antagonists, such as ZM241385 (listed above) or caffeine, show significantly delayed tumor growth due to T-cells resistant to inhibition. (wikipedia.org)
- The activation of RhoA and its effector Rho kinases (ROCK) after the ligation of these inhibitors to the corresponding receptors has been shown to be a key element for axonal growth inhibition. (eurekaselect.com)
- Cellular adenosine transporte uptake of oTR but not adenosine receptors was involved in the growth inhibition. (alliedacademies.org)
- This mechanism is distinct from PDE and adenosine receptor inhibition. (statpearls.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)
- In particular, the activation of the A3 receptor on this cellular type leads to the inhibition of degranulation and superoxide anion production with consequent anti-inflammatory effects. (unife.it)
- Inhibition of COX1, as with acetylsalicylic acid, and inhibition or absence of GPIIb/IIIa receptor, as seen in Glanzmann's thrombasthenia, will reduce platelet aggregation in response to arachidonic acid. (wikipedia.org)
- 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)
- It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol, the active agent in cannabis, and other phytocannabinoids (plant cannabinoids). (wikipedia.org)
- NOP activation also causes indirect inhibition of opioid receptors MOP and KOP, resulting in anti-opioid activity in certain tissues. (wikipedia.org)
- Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. (ovid.com)
- The effects of adenosine, CPA and ATP were inhibited by DPCPX, a selective adenosine A1 receptor antagonist. (ovid.com)
- The haemodynamic effects of adenosine are thought to result in part from a release of mast cell amines via A3 receptor stimulation. (hindawi.com)
- Effects of Adenosine Receptor Antagonists on the In Vivo LPS-Induced Inflammation Model of Parkinson's Disease. (biomedsearch.com)
- Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. (wikipedia.org)
- From the 1980s onwards, these effects of adenosine have been used in the treatment of patients with supraventricular tachycardia. (wikipedia.org)
- Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. (drugbank.ca)
- The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. (eurekaselect.com)
- A nucleotidase inhibitor and A2a adenosine receptor antagonist inhibited the apoptotic supernatant-induced gene expression, suggesting AMP was metabolized to adenosine by an ecto-5'-nucleotidase expressed on macrophages, to activate the macrophage A2a adenosine receptor. (elifesciences.org)
- 1. A method of enhancing an immune response in a host, comprising administering to the host an A.sub.2a receptor antagonist in combination or alternation with a checkpoint inhibitor. (patents.com)
- Acid pump antagonists (APAs) or potassium-competitive acid blockers (PCABs) are a third type of inhibitor that blocks acid secretion by binding to the K+ active site. (wikipedia.org)
- Our research led to the identification of ( S )- 1 with high potency (0.5 nM) and selectivity as an A 3 AR antagonist. (rsc.org)
- The ability of G protein-coupled receptors (GPCRs) to form dimers, and particularly heterodimers, offers potential for targeted therapeutics with improved selectivity. (aspetjournals.org)
- 200-fold selectivity versus Adenosine A1-R, Adenosine A2A-R and Adenosine A2B-R. (scbt.com)
- Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. (drugbank.ca)
- It binds to adenosine A2B receptors to prevent bronchoconstriction by inhibiting the release of mediators like histamine and leukotrienes from mast cells. (statpearls.com)
- It preferently binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present basically in heart cells. (wikipedia.org)
- As shown in the chart above, methoctramine binds preferently to M2 receptors, found mostly in the parasympathetic nerves and atria. (wikipedia.org)
- Collagen is added to the sample-saline mix, and binds to collagen-receptors on platelets. (wikipedia.org)
- The histamine binds to H2 receptors on the parietal cell, activating a cAMP-dependent pathway which causes the enzyme to move from the cytoplasmic tubular membranes to deeply folded canaliculi of the stimulated parietal cell. (wikipedia.org)
- The E1 conformation binds a phosphate from ATP and hydronium ion on the cytoplasmic side. (wikipedia.org)
- The E2 conformation binds potassium, and reverts to the E1 conformation to release phosphate and K+ into the cytoplasm where another ATP can be hydrolyzed to repeat the cycle. (wikipedia.org)
- Both eyes of OHT or pONT were intravitreally injected with either 2-Cl-IB-MECA, PBS (vehicle) or 1.2 µM 2-Cl-IB-MECA + 1.2 µM MRS 1220 (A3AR antagonist) immediately before surgery. (arvojournals.org)
- Rats treated with both A3AR agonist and antagonist did not show significant difference from insult alone. (arvojournals.org)
- This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. (elsevier.com)
- The adenosine receptors are commonly known for their antagonists caffeine and theophylline , whose action on the receptors produces the stimulating effects of coffee , tea and chocolate . (wikipedia.org)
- Caffeine keeps you awake by blocking adenosine receptors. (wikipedia.org)
- The encoded protein (the A2A receptor) is abundant in basal ganglia, vasculature, T lymphocytes, and platelets and it is a major target of caffeine, which is a competitive antagonist of this protein. (wikipedia.org)
- Moreover, LPS-induced decrease in the striatal A(2A) receptor density was increased by caffeine and KW6002. (biomedsearch.com)
- 2007 ). Epidemiological studies have indicated an inverse relationship between the consumption of caffeine, a non-selective adenosine receptor antagonist, and the risk of developing PD (Ross et al. (biomedsearch.com)
- 0.05) without altering the hyperaemic response while the A2A adenosine receptor antagonist 8-(3-chlorostyryl) caffeine (1 wM) did not alter CFRs in both groups. (edu.au)
- Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this criteria. (wikipedia.org)
- Macrophages express membrane proteins that function as receptors for PtdSer (e.g. (elifesciences.org)
- The activity of the encoded protein, a G protein-coupled receptor family member, is mediated by G proteins which activate adenylyl cyclase, which induce synthesis of intracellular cAMP. (wikipedia.org)
- A2A and A2B ARs are Gs-coupled, while A1 and A3 ARs inhibit cAMP production via Gi proteins. (bvsalud.org)
- The extent to which this finding applies to other G protein-coupled receptors and their interaction with different G proteins is unknown. (aspetjournals.org)
- This was true even when the receptor was shown, in the same assay, to exist in two different conformational states coupled to two different G proteins. (aspetjournals.org)
- Nucleoside transporters (NTs) are a group of membrane transport proteins which transport nucleoside substrates including adenosine across the membranes of cells and/or vesicles. (wikipedia.org)
- ATP is crucial for ALOX5's metabolic activity A proline-rich region (residues 566-577), sometimes termed a SH3-binding domain, which promotes its binding to proteins with SH3 domains such as Grb2 and may thereby link the enzyme's regulation to tyrosine kinase receptors. (wikipedia.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)
- The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it. (wikipedia.org)
- The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it. (wikipedia.org)
- The PTGER3 gene is located on human chromosome 1 at position p31.1 (i.e. 1p31.1), contains 10 exons, and codes for a G protein coupled receptor (GPCR) of the rhodopsin-like receptor family, Subfamily A14 (see rhodopsin-like receptors#Subfamily A14). (wikipedia.org)
- The β-adrenoceptor was the first G protein-coupled receptor the gene of which was cloned. (wikipedia.org)
- The CB1 receptor is encoded by the gene CNR1, located on human chromosome 6. (wikipedia.org)
- The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. (wikipedia.org)
- The CB2 receptor is encoded by the CNR2 gene. (wikipedia.org)
- Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1). (wikipedia.org)
- The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene. (wikipedia.org)
- We have synthesized the first P2Y1 receptor-selective antagonists through functionalization of adenine nucleotides. (nih.gov)
- The roles of the 1-, 2- and 3-ARs as well as NO were explored by using the selective antagonists CGP-20712A (300 nM), ICI -18551 (50 nM), SR59230A (100 nM) and NOS inhibitors L-NAME (50 μM) or LNNA (50 μM) respectively. (sun.ac.za)
- The role of adenosine and the adenosine A1, A3, A2A and A2B receptors was studied by using adenosine deaminase and the selective antagonists DPCPX (1 μM), MRS 1191(1 μM), ZM241385 (1 μM) and MRS1754 (1 μM). (sun.ac.za)
- The relative potencies of agonists for the A2B adenosine receptor could only be tested by measurement of receptor-stimulated adenylyl cyclase activity. (biomedsearch.com)
- 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)
- Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits. (wikipedia.org)
- Nucleoside-derived antagonists to A3 adenosine receptors lower mouse intraocular pressure and act across species. (edu.hk)
- Adenosine, a purine nucleoside found at high levels in solid tumors, is able to suppress the recognition/adhesion and effector phases of killer lymphocyte-mediated tumor cell destruction. (nih.gov)
- Adenosine is a purine nucleoside, responsible for the regulation of a wide range of physiological and pathophysiological conditions by binding with four G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B and A3 adenosine receptors (ARs). (eurekaselect.com)
- Adenosine is a purine nucleoside composed of a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond. (wikipedia.org)
- This receptor has an inhibitory function on most of the tissues in which it is expressed. (wikipedia.org)
- EP3 is classified as an inhibitory type of prostanoid receptor based on its ability, upon activation, to inhibit the activation of adenyl cyclase stimulated by relaxant types of prostanoid receptors viz. (wikipedia.org)
- Structure-based discovery of selective positive allosteric modulators of antagonists for the M 2 muscarinic acetylcholine receptor. (nih.gov)
- A1 adenosine receptor agonists, antagonists, and allosteric modulators. (eurekaselect.com)
- The CB1 receptor possesses an allosteric modulatory binding site. (wikipedia.org)
- It is an allosteric modulator of the μ- and δ-opioid receptors as well. (wikipedia.org)
- T-cell proliferation in response to mitogenic anti-CD3 antibody was impaired in the presence of 10 microM adenosine (plus coformycin to inhibit endogenous adenosine deaminase). (nih.gov)
- The A1, together with A2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
- Catecholamine depletion with reserpinisation enhances the responsiveness of the coronary resistance vessels to endogenous adenosine through activation of the A2B adenosine receptor. (edu.au)
- They are all prodrugs which need to be converted to an active metabolite in-vivo to inhibit the P2Y12 receptor. (wikipedia.org)
- On the other hand novel drugs like ticagrelor (Brilique®) and cangrelor (Kengrexal®) are non-thienopyridines and reversibly inhibit P2Y12 meaning they act directly on the receptor without the requirement of metabolic activation and display faster onset and offset of action. (wikipedia.org)
- Antiplatelet drugs like clopidogrel and prasugrel irreversibly inhibit the ADP receptor P2Y12, leading to a decreased ADP-induced platelet aggregation. (wikipedia.org)
- Drugs that inhibit the GPIIb/IIIa receptor, e.g. eptifibatide, can also reduce or eliminate the ADP-induced platelet response. (wikipedia.org)
- H2-receptor antagonists, like cimetidine (Tagamet), inhibit the signaling pathway that leads to activation of the ATPase. (wikipedia.org)
- The CB1 receptor is expressed pre-synaptically at both glutaminergic and GABAergic interneurons and, in effect, acts as a neuromodulator to inhibit release of glutamate and GABA. (wikipedia.org)
- Responses to P2X-receptor stimulation result from activation of nonselective cation channels in the cell membrane. (cdc.gov)
- Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. (wikipedia.org)
- In the rat isolated omental mast cell we conclude that degranulation is an indirect result of A 1 receptor stimulation. (hindawi.com)
- We also noted that the A3 receptor stimulation led to increased levels of MMP9 protein in cellular extracts of U87MG cells, through phosphorylation of ERK1 / 2, JNK, Akt / PKB and the transcription factor AP-1. (unife.it)
- Finally, as for the physiological relevance of the A3 receptor-mediated stimulation of MMP-9 we found that the A3 agonist was responsible for an increase of the invasive ability of U87MG cells. (unife.it)
- In contrast, Beta-1 adrenergic receptors are coupled only to Gs, and stimulation of these results in a more diffuse cellular response. (wikipedia.org)
- In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol may be employed. (wikipedia.org)
- Heteromers consisting of adenosine A1/A2A, dopamine D2/A2A and D3/A2A, glutamate mGluR5/A2A and cannabinoid CB1/A2A have all been observed, as well as CB1/A2A/D2 heterotrimers, and the functional significance and endogenous role of these hybrid receptors is still only starting to be unravelled. (wikipedia.org)
- The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease. (wikipedia.org)
- As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. (wikipedia.org)
- Nociceptin is thought to be an endogenous antagonist of dopamine transport that may act either directly on dopamine or by inhibiting GABA to affect dopamine levels. (wikipedia.org)
- Adenosine Receptors: Structure, Distribution, and Signal Transduction. (eurekaselect.com)
- the respective roles of the A1-, A2-, A3-adenosine receptors as well as the involvement of the PI3-K/PKB/Akt and ERKp44/p42 signal transduction pathways, in the cardioprotective phenomemon of -adrenergic preconditioning and (iv) the contribution of the mitochondrial KATP channels (mKATP), reactive oxygen species and NO to the mechanism of -AR-induced cardioprotection. (sun.ac.za)
- Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues. (wikipedia.org)
- Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. (wikipedia.org)
- Adenozinski A 3 receptori je G protein-spregnuti receptor koji učestvuje u mnogobrojnim ćelijskim signalnim putevima i fiziološkim funkcijama. (wikipedia.org)
- This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alpha helices. (wikipedia.org)
- The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. (wikipedia.org)
- In this role, A2AR functions similarly to programmed cell death-1 (PD-1) and cytotoxic t-lymphocyte associated protein-4 (CTLA-4) receptors, namely to suppress immunologic response and prevent associated tissue damage. (wikipedia.org)
- G protein-coupled receptor (GPCR) family members are integral to cell-cell communication and transduce signals to a wide range of chemical messengers. (aspetjournals.org)
- This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. (wikipedia.org)
- Adenosine acts as a powerful signaling molecule via four distinct G protein-coupled receptors, designated A1, A2A, A2B and A3 adenosine receptors (ARs). (bvsalud.org)
- Adenosine A3 receptors are G protein-linked receptors that functionality in body structure and intracellular signaling and are inquisitive about inflammatory responses and mediating cellphone proliferation and mobilephone demise. (stainlessqa.com)
- The results of this study, obtained by using real time RT-PCR and Western blotting, show that adenosine is able to increase both MMP9 mRNA and protein levels through the activation of the A3 adenosine receptor. (unife.it)
- Overall, these results suggest that adenosine, through activation of the A3 receptor, modulates MMP9 protein levels and plays a role in the invasion of U87MG cells. (unife.it)
- The P2Y12 receptor is a surface bound protein found on blood platelets. (wikipedia.org)
- They belong to G protein-coupled purinergic receptors (GPCR) and are chemoreceptors for ADP. (wikipedia.org)
- The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). (wikipedia.org)
- The cannabinoid type 1 receptor, often abbreviated as CB1, is a G protein-coupled cannabinoid receptor located primarily in the central and peripheral nervous system. (wikipedia.org)
- The receptor may exist as a homodimer or form heterodimers or other GPCR oligomers with different classes of G-protein-coupled receptors. (wikipedia.org)
- Upon activation, CB1 receptor exhibits its effects mainly through activation of Gi, which decreases intracellular cAMP concentration by inhibiting its production enzyme, adenylate cyclase, and increases mitogen-activated protein kinase (MAP kinase) concentration. (wikipedia.org)
- Repeated administration of receptor agonists may result in receptor internalization and/ or a reduction in receptor protein signalling. (wikipedia.org)
- As is commonly seen in G protein-coupled receptors, the CB2 receptor has seven transmembrane spanning domains, a glycosylated N-terminus, and an intracellular C-terminus. (wikipedia.org)
- The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined by making a fusion protein with lysozyme to increase the hydrophilic surface area of the protein for crystal contacts. (wikipedia.org)
- Cannabidiol has been found to act as an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain. (wikipedia.org)
- 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 126.96.36.199) that plays a role in cellular energy homeostasis. (wikipedia.org)
- Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). (wikipedia.org)
- The figurative elements of blood are important substrates on which adenosine plays multiple physiological functions. (unife.it)
- Purinergic receptors are specific classes of membrane receptors that mediate various physiological functions such as the relaxation of gut smooth muscle, as a response to the release of ATP or adenosine. (wikipedia.org)
- Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute coronary syndrome (ACS) or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a stroke. (wikipedia.org)
- Adenosine diphosphate (ADP) is a platelet agonist. (wikipedia.org)
- During the blood clotting process, adenosine diphosphate (ADP) plays a crucial role in the activation and recruitment of platelets and also ensures the structural integrity of thrombi. (wikipedia.org)
- Sajjadi FG, Firestein GS: cDNA cloning and sequence analysis of the human A3 adenosine receptor. (drugbank.ca)
- Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG: Molecular cloning and characterization of the human A3 adenosine receptor. (drugbank.ca)
- Structure of the adenosine-bound human adenosine A 1 receptor-G i complex. (nih.gov)
- A pyridine derivative that acts as a highly selective antagonist of A 3 receptor with excellent potency in both humans and rodents (K i = 18.9 nM for human A 3 R, and 113 nM for rat A 3 R). Exhibits only a trivial antagonistic activity towards A 1 and A 2A receptors (K i = 15.6 µM and 2.05 µM for rat A 1 R and A 2A R, respectively). (merckmillipore.com)
- Borea PA, Gessi S, Merighi S, Varani K. Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? (eurekaselect.com)
- Several potent and selective A3 AR antagonists, e.g. 7, 8, 17 and 22 (Ki values of 5-9 nM at the human A3 AR) were prepared, which were much less potent at the rat orthologue. (bvsalud.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)
- In the human heart, adenosine functions as an autacoid in the regulation of various cardiac functions such as heart rate, contractility, and coronary flow. (wikipedia.org)
- Studies using animals genetically engineered to lack EP3 and supplemented by studies examining the actions of EP3 receptor antagonists and agonists in animals as well as animal and human tissues indicate that this receptor serves various functions. (wikipedia.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)
- Approximately 360 amino acids comprise the human CB2 receptor, making it somewhat shorter than the 473-amino-acid-long CB1 receptor. (wikipedia.org)
- The human CB1 and the CB2 receptors possess approximately 44% amino acid similarity. (wikipedia.org)
- The amino acid sequence of the CB2 receptor is less highly conserved across human and rodent species as compared to the amino acid sequence of the CB1 receptor. (wikipedia.org)
- Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates. (wikipedia.org)
- Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused mainly on the role of adenosine receptors in the heart, and led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest. (wikipedia.org)
- After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. (drugbank.ca)
- A non-sedating ophthalmic antihistamine that antagonizes histamine H1 receptors (IC 50 = 1.58 nM) and prevents the release of pro-inflammatory mediators from mast cells and eosinophils. (thomassci.com)
- As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near future in order to provide more selective therapeutic modalities for the treatment of diseases such as asthma, cardiovascular diseases, inflammation, pain, etc. (eurekaselect.com)
- Recent studies have shown the presence of A3 receptors on neutrophils, which represent the majority of circulating leukocytes and are the first cells to be recruited into a site of tissue inflammation in defending the body against infection. (unife.it)
- A3 adenosine receptor agonists at low concentrations and P2Y6 receptor agonists have antiapoptotic effects. (nih.gov)
- Recent research, however, led to find the mentioned specialty dubious, rising the possibility of it binding to other types of receptors, such as nicotinic ACh receptors -at micromolar concentrations- or adenosine A3. (wikipedia.org)
- There is preclinical evidence to suggest that cannabidiol may reduce THC clearance, modestly increasing THC's plasma concentrations resulting in a greater amount of THC available to receptors, increasing the effect of THC in a dose-dependent manner. (wikipedia.org)
- It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions. (wikipedia.org)
- Purinergic receptors, represented by several families, are among the most abundant receptors in living organisms and appeared early in evolution. (wikipedia.org)
- There are three known distinct classes of purinergic receptors, known as P1, P2X, and P2Y receptors. (wikipedia.org)
- After binding onto a specific purinergic receptor, adenosine causes a negative chronotropic effect due to its influence on cardiac pacemakers. (wikipedia.org)
- They include the NMDA receptors, AMPA receptors, P2X7 purinergic receptors, pannexin channels (Panx1), transient receptor potential (TRP) channels, and acid-sensing ion channels (ASICs). (wikipedia.org)
- Tumor-associated adenosine may act through the same mechanism to impair the development of tumor-reactive T cells in cancer patients. (nih.gov)
- Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function. (wikipedia.org)
- The discovery of the receptors and downstream signals of these inhibitors enabled further understanding of the mechanism underlying the failure of axonal regeneration. (eurekaselect.com)
- It may potentiate THC's effects by increasing CB1 receptor density or through another CB1 receptor-related mechanism. (wikipedia.org)
- Therefore, this review focuses on mechanisms of intracellular delivery, including direct internalization and endocytosis, as well as factors such as targeting moiety, target receptor, and size, shape, and surface properties of the drug carrier that can influence uptake process. (eurekaselect.com)
- These interactions induce a conformational change in the receptor structure, which triggers the activation of various intracellular signaling pathways. (wikipedia.org)
- During brain ischemia, glutamate is released in excess from the presynaptic terminal, leading to the uncontrollable opening of the glutamate receptors, including the NMDA and AMPA receptors, which allows for an excessive influx of Ca2+ into the intracellular environment. (wikipedia.org)