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.
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.
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.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
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.
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.
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.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
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.
An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.
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).
Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.
Purine bases found in body tissues and fluids and in some plants.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
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.
A family of hexahydropyridines.
Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.
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.
Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.
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.
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.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.
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.
Agents inhibiting the effect of narcotics on the central nervous system.
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.
Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.
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.
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.
Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
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.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
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.
A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.
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.
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.
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.
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.
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.
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. 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.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.
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.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
Compounds with BENZENE fused to AZEPINES.
N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.
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.
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.
Drugs that bind to and block the activation of PURINERGIC RECEPTORS.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.
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.
Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.
A group of compounds that contain the structure SO2NH2.
A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.
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 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).
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.
Seven membered heterocyclic rings containing a NITROGEN atom.
An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
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.
Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.
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)
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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.
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)
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.
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.
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.
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.
A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.
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.
The observable response an animal makes to any situation.
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.
The presence of bacteria, viruses, and fungi in water. This term is not restricted to pathogenic organisms.
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.
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.
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.
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.
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.
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.
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.
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.
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.
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.
A genus of bacteria causing GRANULOMA INGUINALE and other granulomatous lesions.
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.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
Injections into the cerebral ventricles.
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.
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.
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.
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
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.
A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.
Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.
An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.
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.
Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.
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.
The rate dynamics in chemical or physical systems.
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.
Use of electric potential or currents to elicit biological responses.
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.
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)
Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.
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)
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.
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.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
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 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.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
Drugs used to cause dilation of the blood vessels.
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.
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.
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).
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.
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.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
Peptides composed of between two and twelve amino acids.
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)
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.
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.
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.
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.
Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.
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.
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.
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.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
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.
The physical activity of a human or an animal as a behavioral phenomenon.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
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.
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.
Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.
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.
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.
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)
Drugs that bind to and activate dopamine receptors.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
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.
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.
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.
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.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
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.
The most common inhibitory neurotransmitter in the central nervous system.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
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.
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)
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.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
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)
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.
AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.
The number of times the HEART VENTRICLES contract per unit of time, usually per minute.
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)
The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.
A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.
Catalyze the hydrolysis of nucleosides with the elimination of ammonia.
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.
Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.
Established cell cultures that have the potential to propagate indefinitely.

Contribution of adenosine to the depression of sympathetically evoked vasoconstriction induced by systemic hypoxia in the rat. (1/257)

Previous studies have shown that systemic hypoxia evokes vasodilatation in skeletal muscle that is mediated mainly by adenosine acting on A1 receptors, and that the vasoconstrictor effects of sympathetic nerve activity are depressed during hypoxia. The aim of the present study was to investigate the role of adenosine in this depression. In anaesthetised rats, increases in femoral vascular resistance (FVR) evoked by stimulation of the lumbar sympathetic chain with bursts of impulses at 40 or 20 Hz were greater than those evoked by continuous stimulation at 2 Hz with the same number of impulses (120) over 1 min. All of these responses were substantially reduced by infusion of adenosine or by graded systemic hypoxia (breathing 12, 10 or 8 % O2), increases in FVR evoked by continuous stimulation at 2 Hz being most vulnerable. Blockade of A1 receptors ameliorated the depression caused by adenosine infusion of the increase in FVR evoked by 2 Hz only and did not ameliorate the depression caused by 8 % O2 of increases in FVR evoked by any pattern of sympathetic stimulation. A2A receptor blockade accentuated hypoxia-induced depression of the increase in FVR evoked by burst stimulation at 40 Hz, but had no other effect. Neither A1 nor A2A receptor blockade affected the depression caused by hypoxia (8 % O2) of the FVR increase evoked by noradrenaline infusion. These results indicate that endogenously released adenosine is not responsible for the depression of sympathetically evoked muscle vasoconstriction caused by systemic hypoxia; adenosine may exert a presynaptic facilitatory influence on the vasoconstrictor responses evoked by bursts at high frequency.  (+info)

Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. (2/257)

Adenosine is a neuromodulator in the nervous system and it has recently been observed that pharmacological blockade or gene disruption of adenosine A(2A) receptors confers neuroprotection under different neurotoxic situations in the brain. We now observed that coapplication of either caffeine (1-25 micro M) or the selective A(2A) receptor antagonist, 4-(2-[7-amino-2(2-furyl)(1,2,4)triazolo (2,3-a)(1,3,5)triazin-5-ylamino]ethyl)phenol (ZM 241385, 50 nM), but not the A receptor antagonist, 8-cyclopentyltheophylline (200 nM), prevented the neuronal cell death caused by exposure of rat cultured cerebellar granule neurons to fragment 25-35 of beta-amyloid protein (25 micro M for 48 h), that by itself caused a near three-fold increase of propidium iodide-labeled cells. This constitutes the first in vitro evidence to suggest that adenosine A(2A) receptors may be the molecular target responsible for the observed beneficial effects of caffeine consumption in the development of Alzheimer's disease.  (+info)

Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats. (3/257)

The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neither L-DOPA nor SCH 58261 given separately modified the reserpine-enhanced tonic or reflex EMG activities in both muscles examined. However, when L-DOPA (25 mg/kg) was given together with SCH 58261 (0.1 mg/kg), a clear synergistic effect was seen on both examined movements and muscles. The present results show that the blockade of adenosine A2A receptors potentiates the antiparkinsonian effect of L-DOPA. Since such an effect was seen in different animal models of Parkinson's disease (PD), it seems that co-administration of SCH 58261 may allow for the lowering of the doses of L-DOPA in clinical practice, which indicates a potential therapeutic value of this compound in the treatment of PD.  (+info)

Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. (4/257)

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)

Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK. (5/257)

Activation of adenosine receptors in folliculostellate (FS) cells of the pituitary gland leads to the secretion of IL-6 and vascular endothelial growth factor (VEGF). We investigated the action of adenosine A2 receptor agonists on IL-6 and VEGF secretion in two murine FS cell lines (TtT/GF and Tpit/F1), and demonstrated a rank order of potency, 5'-N-ethylcarboxamidoadenosine (NECA)>2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine>adenosin e, suggesting mediation via the A2b receptor. NECA-mediated IL-6 release was inhibited by the PLC inhibitor 1-[6-((17beta-3-methoxyestra-1,3,5(10)-tiene-17-yl)amino)hexyl]-1H-pyrrole-2,5-di one, the PI3 kinase inhibitor wortmannin and the PKC inhibitors bisindolylmaleimide 1 and bisindolymaleimide X1 HCl (Ro-32-0432). NECA-mediated IL-6 release was attenuated (<50%) by the extracellular signal-regulated kinase MAPK inhibitor 2'-amino-3'-methoxyflavone, and completely (>95%) inhibited by the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole. NECA stimulates p38 MAPK phosphorylation that is inhibited by Ro-32-0432 but not by wortmannin. Dexamethasone inhibits NECA-stimulated IL-6 and VEGF secretion. These findings indicate that adenosine can stimulate IL-6 secretion in FS cells via the A2b receptor coupled principally to PLC/PKC and p38 MAPK; such an action may be important in the modulation of inflammatory response processes in the pituitary gland.  (+info)

Possible targeting of G protein coupled receptors to manipulate inflammation in vivo using synthetic and natural ligands. (6/257)

Cyclic AMP elevating Gs protein coupled receptors were considered for a long time to be immunosuppressive. One of these receptors, adenosine A(2A) receptor, was implicated in a physiological mechanism that down regulates inflammation and protects tissues from excessive immune mediated damage. Targeting of these receptors by selective agonists may lead to better protocols of anti-inflammatory treatments. At the same time inhibiting the Gs protein coupled mediated signalling with antagonists could be explored in studies of approaches to enhance inflammation and tissue damage. Enhancement of targeted tissue damage is highly desirable when it is cancerous tissue, while enhancement of inflammatory events might be desirable in the development of new vaccine adjuvants.  (+info)

Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. (7/257)

Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.  (+info)

Antinociceptive effects of novel A2B adenosine receptor antagonists. (8/257)

Caffeine, an adenosine A1, A2A, and A2B receptor antagonist, is frequently used as an adjuvant analgesic in combination with nonsteroidal anti-inflammatory drugs or opioids. In this study, we have examined the effects of novel specific adenosine receptor antagonists in an acute animal model of nociception. Several A2B-selective compounds showed antinociceptive effects in the hot-plate test. In contrast, A1- and A2A-selective compounds did not alter pain thresholds, and an A3 adenosine receptor antagonist produced thermal hyperalgesia. Evaluation of psychostimulant effects of these compounds in the open field showed only small effects of some antagonists at high doses. Coadministration of low, subeffective doses of A2B-selective antagonists with a low dose of morphine enhanced the efficacy of morphine. Our results indicate that analgesic effects of caffeine are mediated, at least in part, by A2B adenosine receptors.  (+info)

The IUPHAR/BPS Guide to Pharmacology. istradefylline ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
In 6-OHDA-lesioned rats, repeated administration produces behavioral sensitization, manifested as a marked increase in l-Dopa-induced contralateral rotations across days of treatment (Henry et al., 1998). Behavioral sensitization has been suggested to predict the development of dyskinesias after chronic treatment with l-Dopa (Tronci et al., 2007). Here, we found that l-Dopa produced behavioral sensitization after only 4 days of treatment in 6-OHDA-lesioned rats. However, when l-Dopa was delivered concurrently with preladenant, the rats displayed no behavioral sensitization for as long as 23 days of treatment. The blockade of behavioral sensitization by preladenant in this model suggests that this agent may not only have antiparkinsonian effects on its own but also may reduce dyskinesias when used in combination with l-Dopa.. Aside from the motor symptoms that characterize PD, there are a collection of nonmotor symptoms that are not treated by current pharmacotherapies. One of the most severe is ...
Major surface area glycoprotein (Msg) one of the most abundant cell surface area protein of in 3 species of cant be cultured promoter activity was measured in luciferase being a reporter gene. different types with infecting human beings infecting rats and infecting mice (7-9). Main surface area glycoprotein (Msg) may be the most abundant proteins in the cell surface area of gene is certainly expressed within an specific cell and that expressed gene is situated downstream of an area termed the upstream conserved series (UCS) (17-21). Although appearance of Msg gene variations continues to be well studied small Istradefylline is known about how exactly expression is governed. In and since intergenic locations are often ~300 to 500 bp lengthy (unpublished observations). This shows that this area may be essential in regulating appearance perhaps through promoter components (22). Although cannot presently end up being cultured for suffered periods advancement of vectors you can use to transfect ...
Test-retest reproducibility study of [C-11]Preladenant. Assessment of stability and variation of the PET measures in healthy volunteers.
Discouraging news this week for the Parkinson s community, as drug giant Merck announced that they will discontinue their program developing a novel therapy for PD called preladenant.
3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile chemical properties, What are the chemical properties of 3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile 86375-28-2, What are the physical properties of 3-(2,4,4-trimethylpentan-2-ylamino)propanenitrile ect.
Structure, properties, spectra, suppliers and links for: N-[3-(2,1,3-Benzothiadiazol-5-ylamino)-2-quinoxalinyl]-4-methylbenzenesulfonamide.
Disclosed are processes for the synthesis of novel compounds that are A.sub.2B adenosine receptor antagonists, having the structure of Formula I or Formula II: ##STR00001## by cyclizing a compound of the formula (3): ##STR00002##
Learn about regadenoson: What is it used for, what you need to know before taking, important warnings and safety info, how to take, side effects and more...
SCH 442416 is a selective adenosine A2A receptor antagonist; binds to human and rat A2A receptors with high affinity (Ki values are 0.048 and 0.5 nM respectively). Displays > 23000-fold selectivity for hA2A over hA1 in vitro with minimal affinity for h
4-((8-amino-3,6,10,13,16,19-hexaazabicyclo(6.6.6)icosane-1-ylamino)methyl)benzoic acid: a bifunctional chelating agent; structure in first source
DESCRIPTION: (Adapted from the Investigators Abstract): Adenosine administered as an aerosol to asthmatics causes bronchoconstriction, while in non-asthmatics adenosine causes bronchodilation. This occurs because the activation of A2B adenosine receptors on sensitized mast cells triggers degranulation, releasing histamine, leukotrienes, and other allergic mediators. A2B adenosine receptors are blocked by theophylline, a xanthine that is effective in treating asthma. However, theophylline is a non-selective antagonist of all four adenosine receptor subtypes and produces side effects due primarily to A1 receptor blockade, including insomnia and diuresis. The incidence of asthma is increasing and current treatment options are limited. New drugs that are potent and selective antagonists of A2B adenosine receptors have great potential for the treatment of asthma and other allergic diseases. Adenosine Therapeutics, LLC owns the first potent and selective A2B antagonists. The purpose of this phase I ...
ALI is one of the leading causes of morbidity and mortality of critical illness with extremely limited therapeutic options. In the present study, we pursued the hypothesis that tissue-specific adenosine signaling events through the A2B adenosine receptor contribute to lung protection and can thus be targeted for ALI treatment. To make progress on this front, we performed a head-to-head comparison of mice with genetic deletion of Adora2b in the myeloid lineage, vascular endothelial cells, or alveolar epithelial cells. Interestingly, we only observed a phenotype in mice with tissue-specific Adora2b deletion in alveolar epithelial cells, closely resembling the observed detrimental effects of global Adora2b deletion during ALI. Interestingly, the injurious effects of our two-hit model where an inflammatory event (i.t. LPS treatment) is followed by injurious mechanical ventilation seem to be supra-additive compared with the effects of injurious ventilation or LPS i.t. alone. Based on these findings ...
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1-1H-Indol-7-yl-3-[5-(2-{thieno[3,2-d]pyrimidin-4-ylamino}ethyl)-1,3-thiazol-2-yl]urea | C20H17N7OS2 | CID 25138117 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
The present invention provides compounds and pharmaceutical compositions that are substituted pyridyl-linked-xantbines of formula I which are selective antagonists of A2B adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.
chemBlink provides information about CAS # 3945-69-5, 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholinium chloride, DMTMM, molecular formula: C10H17ClN4O3.
Methanol,[(4,6-dimethyl-1,3,5-triazin-2-yl)amino]-(9ci)/ACM84591888 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
4-(Methylthio)-1,3,5-triazin-2-amine/AFI27282899 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
The adenosinergic pathway plays a critical role in cancer development and progression, as well as in drug resistance to chemotherapy and/or targeted-therapy. The goal of this PhD thesis was to investigate and fully ...
A review. The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain G protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various species, including rat and human, and its sequences are highly similar across species, ranging from 85% identity between human and mouse and 95% identity between rat and mouse. The A2B receptors show a ubiquitous distribution, the highest levels are present in cecum, colon and bladder, followed by blood vessels, lung, eye and mast cells. Through A2B receptors adenosine seems to cause mast cells degranulation, vasodilation, cardiac fibroblast proliferation, inhibition of Tumor Necrosis Factor (TNF-α), increased synthesis of interleukin-6 (IL-6), stimulation of Cl- secretion in intestinal epithelia and hepatic glucose prodn. Hence, A2B adenosine receptor agonists could be useful ...
Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = ...
Particularly preferably, Z21 is 2,4-dichloro-1,3,5-triazin-6-ylf 2-chloro-4-(3-(2-suifatoethylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-chloro-4-(4-(2-su!fatoethy!sulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-chloro-4-(3-(vinylsulfonyl)-phenylarnino)-1 t3,5-triazin-6-yl, 2-chloro4-(4-(vinylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl, 2-ch!oro-4-(N-methy!-N-(2-(2-sulfatoethylsulfonyl)-ethy!)-amino)-1,3,5-triazin-6-yl, 2-ch!oro-4-(N-phenyl-N-(2-(2-sulfatoethylsulfonyl)-ethyl)-amino)-1,3,5-tria2in-6-yl, 2-fluoro-4-morpholino-1,3,5-triazin-6-yI, 2-fluoro-4-(2-sulfophenyl-amino)-1,3,5-triazin-6-yl, 2-fluoro-4-(3-sulfophenylamino)-1,3,5-triazin-6-yl, 2-fluoro-4-(4-sulfophenylamino)-1,3,5-triazin-6-yl, 2-fiuoro-4-(3-trimethylammonio-phenylamino)-1,3,5-triazin-6-ylf 2-fIuoro-4-(4-trirnethylammoniophenylamino)-1,3,5-triazin-6-yl, 2-fluoro-4-(3-(2-sulfatoethylsulfonyl)-phenylamino)-1,3,5-triazin-6-yl( 2-fluoro-4-(4-(2-sulfatoethylsulfonyl,-phenylamino)-1 f3,5-triazin-6-yl, ...
3-Fluoro-5-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol | C11H16FNO3 | CID 12780318 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
2-[4,6-Bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol 2725-22-6 MSDS report, 2-[4,6-Bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol MSDS safety technical specifications search, 2-[4,6-Bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol safety information specifications ect.
This trial will investigate the effects of single doses of preladenant and placebo on the dyskinesia and antiparkinsonian actions of a levodopa infusion.
The development, maintenance and repair of the skeletal system are dependent on the differentiation of both chondrocytes and osteoblasts from their common progenitor, the mesenchymal stem cell (MSC). The A2B adenosine receptor (A2BAR) is a G-protein-coupled receptor that signals by increasing cAMP and/or activating phospholipase C signaling. Considering the published roles of cAMP on MSC differentiation, and our finding that the expression of the A2BAR is induced following injury, we hypothesized that ablation or activation of the A2BAR impacts the differentiation of osteoblasts and chondrocytes and that this would manifest as changes in skeletal development and bone fracture repair. Activation of the A2BAR increased the differentiation of bone marrow-derived MSCs to osteoblasts by increasing mRNA expression of the transcription factors runt-related transcription factor 2 (Runx2) and Sp7 transcription factor (Osterix), which are essential for osteoblast differentiation. To examine the effect of ...
TY - JOUR. T1 - Attenuation of chronic pulmonary inflammation in A2B adenosine receptor knockout mice. AU - Zaynagetdinov, Rinat. AU - Ryzhov, Sergey. AU - Goldstein, Anna E.. AU - Yin, Huiyong. AU - Novitskiy, Sergey V.. AU - Goleniewska, Kasia. AU - Polosukhin, Vasiliy V.. AU - Newcomb, Dawn C.. AU - Mitchell, Daphne. AU - Morschl, Eva. AU - Zhou, Yang. AU - Blackburn, Michael R.. AU - Peebles, R. Stokes. AU - Biaggioni, Italo. AU - Feoktistov, Igor. PY - 2010/5/1. Y1 - 2010/5/1. N2 - Pharmacologic evidence suggests that activation of A2B adenosine receptors results in proinflammatory effects relevant to the progression of asthma, a chronic lung disease associated with elevated interstitial adenosine concentrations in the lung. This concept has been challenged by the finding that genetic removal of A2B receptors leads to exaggerated responses in models of acute inflammation. Therefore, the goal of our study was to determine the effects of A2B receptor gene ablation in the context of ...
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This work done by an eminent group in the area raises concerns over the use of regadenoson for clinical stress testing, whether done by PET or SPECT. Invasive and pharmacologic studies had previously demonstrated peak regadenoson effect at approximately 1-2 minutes after injection, consistent with the findings of the present study. Stress labs which are not already following a 1- to 2-minute delay may wish to consider introducing one.. There are several reasons to view these results with caution, however. First, many prior studies had compared regadenoson to other vasodilators using a variety of techniques including PET, SPECT, and invasive methods. In general, no significant differences or only minimal differences, below the level of clinical relevance, were observed. The reasons for the discrepancies are unclear.. One longstanding concern with regards to regadenoson has been the use of a single fixed dose without weight adjustment, as is usually done for other vasodilators. The investigators ...
Approximately 250 patients who are referred for a nuclear stress testing of the heart with regadenoson (Lexiscan®) will be recruited to participate in the study. Following regadenoson (administered as part of a stress routine test protocol) participants will receive either aminophylline (75 mg - intravenously) or a matching inactive placebo (sterile salt water) injection. Participants will be surveyed for gastrointestinal symptoms and other side effects related to regadenoson. The frequency and severity of such side effects will be compared between the two study groups (aminophylline vs. placebo ...
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Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining. Manufactured by Astellas and FDA approved April 10, 2008.
We investigated the electrophysiological effects of cardiac hypertrophy induced by different experimental models. Comparison of the action potentials of hypertrophied and control rat hearts reveals a pronounced prolongation of the action potential fo
Page contains details about film of 3,9-di(9H-carbazol-9-yl)benzo-[d]benzo[4,5]imidazo[2,1-b]thiazole doped with 10-(4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9,9-diphenyl-9,10-dihydroacridine . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
Microwave Induced Synthesis of 3-Aryl-6-(6-/8-substituted 4-chloroquinoline-3-yl) - s -triazolo [3,4-|em|b]|/em| −1,3,4-thiadiazoles | Ren-Zhong Qiao; Xta-Ptag Hui; Peng-Fei Xu; Zi-Yi Zhang; Dong-Liang Cheng | download | BookSC. Download books for free. Find books
Corresponding Author: Anaclet Ngezahayo Department of Cell Physiology and Biophysics, Institute of Cell Biology and Biophysics, Leibniz University Hannover, Herrenhäuser Straße 2, Hannover, 30419 (Germany ...
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The low-affinity A2B receptor is known to mediate proinflammatory effects of adenosine by up-regulating production of cytokines and growth factors. This view has been supported by a large body of evidence provided by pharmacological analysis of adenosine-dependent cytokine and growth factor secretion in various cells, tissues, and organs (8, 11, 13, 18, 31, 32, 33, 34, 35, 36, 37, 38). Pharmacological inhibition of A2B receptors significantly reduced elevations in proinflammatory cytokines as well as mediators of airway remodeling induced by high adenosine levels in the lungs of ADA-deficient mice (8). In the ragweed allergic mouse model, A2B antagonism plays an important role in inhibition of airway reactivity and inflammation (39, 40). In agreement with data obtained in these animal models of pulmonary inflammation, stimulation of A2B receptors in the human mast cell line HMC-1 was shown to induce secretion of proinflammatory Th2 cytokines IL-4 and IL-13 (11, 12), as well as angiogenic factors ...
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Action adenosinergic funds due to a direct interaction with adenozinovymi (purine) receptors and indirect effect on the disintegration and accumulation of adenosine (one of the purine neuromodulators). Specialized purine receptors (post - and presynaptic), divided into the P1 receptors (highly sensitive to adenosine) and P2 receptors (more sensitive to ATP). Both types are found in the Central nervous system, cardiovascular and respiratory system, lymph and platelets, etc.. It is known that adenosine has mainly cardiovascular effects, manifested by vasodilatation (with improvement of microcirculation and reduction of platelet aggregation) and negative Ino-, Chrono and dromotropony effects on the heart associated with inhibition of intracellular transport of calcium ions. A number of drugs (dipyridamole, papaverine, etc.) affect the metabolism of adenosine, contribute to its accumulation in the myocardium or potentiate the effect; used as koronarolitikov the disease ...
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View mouse Adora1 Chr1:134199225-134235431 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
View mouse Adora2a Chr10:75316877-75334784 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
"Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, ... CGS-15943 is a drug which acts as a potent and reasonably selective antagonist for the adenosine receptors A1 and A2A, having a ... It was one of the first adenosine receptor antagonists discovered that is not a xanthine derivative, instead being a ... Holtzman SG (1991). "CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and ...
Schwabe, U; Ukena, D; Lohse, MJ (September 1985). "Xanthine Derivatives as Antagonists at A1 and A2 Adenosine Receptors". ... It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor. Xanthine "International Non-Proprietary Names. ...
These signaling elements include thromboxane A2, receptor type α, phospholipase Cβ3, and IP3 receptors. Signalization in ... It belongs to the homologous family of glycoprotein IIb-IIa antagonists. Kistrin has an adhesion site that binds to GP IIb-IIIa ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). ... TX2 effects are mediated by G protein-coupled receptors, subtypes TPα and TPβ. Both receptors mediate phospholipase C ...
... a potent and selective adenosine A2 receptor antagonist.". Eur. J. Pharmacol. 267 (3): 335-41. PMID 8088373. doi:10.1016/0922- ... 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): ... 1994). "Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells.". Biochem. Biophys. Res. Commun. ...
The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ... have a purine structure and bind to some of the same receptors as adenosine. Methylxanthines act as competitive antagonists of ... All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... Adenosine is believed to be an anti-inflammatory agent at the A2A receptor. Topical treatment of adenosine to foot wounds in ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... GR-127,935 (mešoviti 5-HT1B/1D antagonist). *LY-310,762. *LY-367,642 ... 5-HT1D receptor (5-hidroksitriptaminski (serotoninski) receptor 1D, HTR1D) je 5-HT receptor. On je kodiran istoimenim genom.[1] ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • ...
nonselective adenosine receptor antagonist,[23] antagonizing A1, A2, and A3 receptors almost equally, which explains many of ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... or rather its adenosine-antagonist behavior).[36] References[edit]. *^ Mandal, Ananya. "Caffeine Pharmacology". Website Medical ... Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth muscles and relaxes the ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... 1997). „Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 ... Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ... Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular ...
Antagonists[edit]. Main article: Receptor antagonist. An antagonist is a chemical that acts within the body to reduce the ... Adenosine. Ado. Adenosine receptors. -. Small: Purine. Adenosine triphosphate. ATP. P2Y receptors. P2X receptors. ... "Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions". American ... NMDA receptors, kainate receptors, AMPARs. Small: Amino acids. Gamma-aminobutyric acid. GABA. GABAB receptors. GABAA receptors ...
Thromboxane A2 receptor. TP. TXA=PGH2,,PGD2=PGE2=PGF2α=PGI2[14]. contractile. Gq alpha subunit. stimulates PLC & IP3; raises Ca ... Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as ... All of the prostanoid receptors are G protein-coupled receptors belonging to the Subfamily A14 of the rhodopsin-like receptor ... There are 9 established prostanoid receptors. The following table gives these receptors: a) full name; b) shortened names; c) ...
... trienoic acid as a thromboxane A2 receptor antagonist with minimal intrinsic activity". British Journal of Haematology. 101 (1 ... to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine ... BLT1 receptor) and its low affinity BLT2 receptor (Kd=23 nM); both receptors are G protein coupled receptors that, when ligand- ... Hicks, A; Monkarsh, S. P.; Hoffman, A. F.; Goodnow Jr, R (2007). "Leukotriene B4 receptor antagonists as therapeutics for ...
... drugs which are selective receptor antagonists of CysLTR1 but not CysLTR2.[20][21][22][23] Models of allergic reactions in ... TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP. *Thromboxane A2 ... leukotriene receptor activity. • cysteinyl leukotriene receptor activity. • galanin receptor activity. Cellular component. • ... "Leukotriene Receptors: CysLT2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
PDP2 receptor antagonists have been shown to allergic reactions induced in the airways mice and sheep as well as the airways ... thromboxane A2. The cyclopentenone prostaglandins, PGJ2, Δ12-PGJ2, and 15-d-Δ12,14-PGJ2 are spontaneously formed or protein- ... with the C5a receptor, Formyl peptide receptor 1, and Formyl peptide receptor 2 receptors. DP2 has little or no such amino acid ... prostaglandin D receptor activity. • G-protein coupled receptor activity. • prostaglandin J receptor activity. • prostaglandin ...
... called H2-receptor antagonists. PPIs are among the most widely sold drugs in the world, and the first one, omeprazole, is on ... Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ... Lucendo AJ, Arias Á, Molina-Infante J (2015). "Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histological ... H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux ...
Adenosine reuptake inhibitor (AdoRI). *Angiotensin II receptor antagonist. *Endothelin receptor antagonist. *NK1 receptor ... Newton, David; Alasdair Thorpe; Chris Otter (2004). Revise A2 Chemistry. Heinemann Educational Publishers. p. 1. ISBN 0-435- ... Major receptor types studied in pharmacology include G protein coupled receptors, ligand gated ion channels and receptor ... Systems, receptors and ligands[edit]. This section needs expansion. You can help by adding to it. (July 2019) ...
血栓素合成酶抑制劑(英語:Thromboxane synthase inhibitors)(雙嘧達莫、吡考他胺(英語:Picotamide)) · 受體拮抗劑(英語:Thromboxane receptor antagonist)(Terutroban( ... ADP受體/P2Y12(英語:P2Y12)抑制劑(英語:Adenosine diphosphate receptor inhibitor)類 ... 阿司匹林低劑量服用時能阻止血小板中血栓素A2的合成,這會在受影響的血小板的
"Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Antagonists: RO1138452. TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP ... prostaglandin receptor activity. • signal transducer activity. • prostaglandin E receptor activity. • protein binding. ... Prostaglandin E2 receptor 4 (EP4). അവലംബം[തിരുത്തുക]. *↑ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000050628 - Ensembl, May ...
Receptor antagonists. *ERA (Atrasentan). *Retinoid X receptor (Bexarotene). *Sex steroid (Testolactone). Other/ungrouped. * ... Adenosine deaminase inhibitor (Pentostatin). *Halogenated/ribonucleotide reductase inhibitors (Cladribine. *Clofarabine. * ...
Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular ... An Adenosine triphosphate (ATP) binding site; ATP is crucial for ALOX5's metabolic activity ... as well as of LTC4 and LTD4 receptor antagonists have proven inferior to corticosteroids as single drug therapy for persistent ...
It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.[28] For the signal to be ... Ephrins (A1, A2, A3, A4, A5, B1, B2, B3). *Erythropoietin (see here instead) ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ... Antagonists: ANA-12. *Cyclotraxin B. *Gossypetin (3,5,7,8,3',4'-HHF) ...
Sunitinib, an inhibitor of the receptors for FGF, PDGF and VEGF is also based on early studies on TKIs aiming at VEGF receptors ... TKIs operate by four different mechanisms: they can compete with adenosine triphosphate (ATP), the phosphorylating entity, the ... Ephrins (A1, A2, A3, A4, A5, B1, B2, B3). *Erythropoietin (see here instead) ... Antagonists: ANA-12. *Cyclotraxin B. *Gossypetin (3,5,7,8,3',4'-HHF) ...
Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular ... An Adenosine triphosphate (ATP) binding site; ATP is crucial for ALOX5's metabolic activity ... as well as of LTC4 and LTD4 receptor antagonists have proven inferior to corticosteroids as single drug therapy for persistent ...
Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 report by DelveInsight offers comprehensive insights of the pipeline ... Pipeline Therapeutics assessment of products for Adenosine A2 Receptor Antagonist The report assesses the active Adenosine A2 ... Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 [Report Updated: 14022018] Prices from USD $1250. 02:34 EDT 21 Mar 2018 ... Features the Adenosine A2 Receptor Antagonist pipeline across the complete product development cycle including all clinical and ...
Effect of A2 Adenosine Receptor Antagonists on Adoptively Transferred Antitumor CD8+ T Cells.. The A2 receptors antagonists ... Effect of A2 Adenosine Receptor Antagonist on Endogenously Developed Antitumor CD8+ T Cells.. The antagonists significantly ... A2 adenosine receptor antagonists also improved the antitumor activity of effector CD8+ T cells specific for the poorly ... T cells and A2 receptor antagonists. (c) ZM241,385, an antagonist of A2AR and A2BR, enhances CD8+ T cell-mediated antitumor ...
Adenosine A2 Receptor Antagonists. Purinergic P1 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ... Participation in a previous adenosine A2A trial.. *Participation in any other investigational drug study within 1 month prior ...
Adenosine A2 Receptor Antagonists. Purinergic P1 Receptor Antagonists. Purinergic Antagonists. To Top ... An Open-Label, Positron Emission Tomography Study to Assess Adenosine A2A Brain Receptor Occupancy of BIIB014 at Multiple Dose ... occupies the brains A2A receptors. Receptor occupancy will be assessed by PET scanning using a radiolabelled tracer. ... Using PET Scans to Study Brain Receptor Occupancy of BIIB014 in Healthy Male Volunteers. The safety and scientific validity of ...
Schwabe, U; Ukena, D; Lohse, MJ (September 1985). "Xanthine Derivatives as Antagonists at A1 and A2 Adenosine Receptors". ... It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor. Xanthine "International Non-Proprietary Names. ...
... and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of ... Adenosine A1 Receptor Antagonists * Adenosine A2 Receptor Antagonists * Dopamine Antagonists * MSX 3 compound ... Co-administration of the adenosine A(2A) receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A(1) antagonist ... The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision ...
... receptor antagonist alternatives to the clinical candidate 8-(3-oxa-tricyclo[3.2.1.0(2,4)]oct-6-yl)-1,3-dipropyl-3,7-dihydro- ... During the search for second-generation adenosine A(1) ... Adenosine A1 Receptor Antagonists* * Adenosine A2 Receptor ... Norbornyllactone-substituted xanthines as adenosine A(1) receptor antagonists Bioorg Med Chem. 2006 Jun 1;14(11):3654-61. doi: ... During the search for second-generation adenosine A(1) receptor antagonist alternatives to the clinical candidate 8-(3-oxa- ...
0 (Adenosine A2 Receptor Antagonists); 0 (Antiparkinson Agents); 0 (Dopamine Agonists); 0 (Indoles); 0 (Purines); 0 (Receptor, ... 0 (Adenosine A2 Receptor Antagonists); 0 (Antiparkinson Agents); 0 (Dopamine Agonists); 0 (Indoles); 0 (Purines); 030PYR8953 ( ... The adenosine A2A receptor antagonist, istradefylline enhances the anti-parkinsonian activity of low doses of dopamine agonists ... The adenosine A2A receptor antagonist, istradefylline improves motor function in patients with advanced Parkinsons disease (PD ...
Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Antagonists (8) • Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS. ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ...
Nonselective adenosine receptor antagonist (Blocks A1, A2, A3 equally). Mechanism: Nonspecific AChRi -,promotes degrdation of ...
"Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, ... CGS-15943 is a drug which acts as a potent and reasonably selective antagonist for the adenosine receptors A1 and A2A, having a ... It was one of the first adenosine receptor antagonists discovered that is not a xanthine derivative, instead being a ... Holtzman SG (1991). "CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and ...
1994) CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischaemic injury in the Mongolian gerbil. Life Sci 55: ... Almost all A2A adenosine receptor agonists and antagonists also have some effects on A1 or A3 receptors (Jacobson et al., 1992 ... 1992) Molecular cloning of the rat A2 adenosine receptor: selective coexpression with D2 dopamine receptors in rat striatum. ... 1994) In vivo and ex vivo effects of adenosine A1 and A2 receptor agonists on platelet aggregation in the rabbit. Eur J ...
... were studied in awake mice lacking one or both of the adenosine A(1) or A(2A) receptors (A(1)R or A(2A)R, respectively) using ... indicating effects of endogenous adenosine. The A(2A)R plays an important role in the modulation of O(2)C and LA by acute and ... Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.. *Lisa ... Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo. * ...
These probes bind to A.sub.2 and A.sub.3 adenosine receptors and aid in quantifying and characterizing the receptors. The ... This application discloses probes for adenosine receptors which are functionalized congeners of the following compound: ##STR1# ... which are antagonists for A-1 and A-2 receptors, these probes are prepared by reacting a fluorescent dye marker, or electron ... Both adenosine and xanthine derivatives bind competitively to A-1 and A-2 adenosine receptors.. UTILITY STATEMENT. The present ...
Additionally, adenosine receptor antagonists blocked mGluR-mediated increases in cAMP accumulation with potencies that were ... highly correlated with their potencies at A2 adenosine receptors. Furthermore, we performed a series of studies that suggest ... We found that adenosine deaminase abolished 1S,3R-ACPD-stimulated cAMP accumulation whereas the adenosine uptake blocker ... Metabotropic glutamate receptors (mGluRs) are coupled to effector systems through GTP-binding proteins (G-proteins) and appear ...
... an adenosine A1 receptor antagonist. Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. ... a selective adenosine A1 receptor antagonist. The selective adenosine A2 and A3 receptors antagonists did not alter the ... Adenosine and ATP exert a negative chronotropic effect in the heart. This study aims to evaluate adenosine and P2 receptors and ... Adenosine A1 receptor activation by adenosine and ATP produces cardiac arrest in the right atrium of Wistar rats predominantly ...
A2 ( straium) Adenosine receptors ... Caffeine is an Antagonist of A1 (cerebral cortex & hippocampus ... 5/12/09 Introduction f Adenosine receptor 1??? Contradictary evidence  activiation of A1 inhibit acetylcholine release  Ach ... As daily caffeine use increases the number of free receptors decreases and the ...
These signaling elements include thromboxane A2, receptor type α, phospholipase Cβ3, and IP3 receptors. Signalization in ... It belongs to the homologous family of glycoprotein IIb-IIa antagonists. Kistrin has an adhesion site that binds to GP IIb-IIIa ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). ... TX2 effects are mediated by G protein-coupled receptors, subtypes TPα and TPβ. Both receptors mediate phospholipase C ...
... including an A2 receptor antagonist caffeine; (6) better tumor rejection observed in A2 receptor antagonist-treated mice is at ... solid tumors are surrounded by extracellular adenosine; (3) A2 adenosine receptors are capable of inhibiting anti-tumor T cells ... The treatment with antagonists of A2 receptors significantly delayed the onset of rapid growth of CL8-1 melanoma, even if ... As it was shown, the dramatic inhibition of tumor neovascularization can be achieved by A2 receptor antagonists [1]. These data ...
... based on experiments involving application of an A2-type adenosine receptor ligand, 5′-N-ethylcarboxamidoadenosine and A2bAR ... antagonists in control and A2bAR KO cells and mice, it was concluded that this receptor can also exert influences via ... Although adenosine activates multiple receptor subtypes (A1, A2a, A2b, and A3 receptors), the adenylyl cyclase stimulatory A2a ... adenosine receptors (A2aARs) are regarded mainly as cardioprotective receptors (1). In general, the A2-type receptors have been ...
Preladenant (SCH 420814) is a novel adenosine A-2 receptor antagonist being evaluated for the treatment of Parkinsons disease ... MK-4305 is a novel orexin receptor antagonist being evaluated in Phase III studies for the treatment of insomnia. Phase IIb ... Vorapaxar (SCH 530348) is an investigational protease activated receptor-1 (PAR-1) antagonist for the treatment of thrombosis. ... Tags: Acute Coronary Syndrome, Adenosine, Allergen, Anacetrapib, Antibodies, Antibody, Asenapine, Asthma, Atherosclerosis, ...
Binding of [3H]KF17837S, a selective adenosine A2 receptor antagonist, to rat brain membranes. ... The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors ... Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A3 receptor subtype. ... N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes. ...
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity. ... 01/01/1993 - "The A1 adenosine antagonist 8-phenyltheophylline (8-PT) potentiated catalepsy induced by NECA, R-PIA and CHA. ". ... Subscribe to New Research on Adenosine-5-(N-ethylcarboxamide) A stable adenosine A1 and A2 receptor agonist. Experimentally, ... 05/01/1998 - "The effect of serotonergic agents was studied on the adenosine A2 receptor agonist NECA-induced catalepsy in mice ...
... lines bound a variety of adenosine agonists and antagonists with affinities characteristic of a brain adenosine A2a receptor. ... lines bound a variety of adenosine agonists and antagonists with affinities characteristic of a brain adenosine A2a receptor. ... The cloned receptor DNA was transfected into human embryonic kidney 293 cells. Stably transfected cell ... The cloned receptor DNA was transfected into human embryonic kidney 293 cells. Stably transfected cell ...
Preladenant (SCH 420814) is a novel adenosine A-2 receptor antagonist being evaluated for the treatment of Parkinsons disease ... MK-4305 is a novel orexin receptor antagonist being evaluated in Phase III studies for the treatment of insomnia. Phase IIb ... Vorapaxar (SCH 530348) is an investigational protease activated receptor-1 (PAR-1) antagonist for the treatment of thrombosis. ... Dalotuzumab (MK-0646) is an antibody targeting the insulin-like growth factor receptor-1 (IGF-1r). Interim analysis of the ...
Adenosine A2 Receptor Antagonists Concept Adenosine A2 Receptor Agonists Concept Receptors, Adenosine A2 ... studies on selective adenosine A2A receptor antagonists. Academic Article Adenosine A2A antagonists as neurotherapeutics: ... Targeting adenosine A2A receptors in Parkinsons disease. Academic Article Adenosine A2A receptors and metabotropic glutamate 5 ... receptor antagonists in Parkinsons disease. Academic Article Mice heterozygous for both A1 and A(2A) adenosine receptor genes ...
Adenosine A2 Receptor Agonists. 1. 2017. 30. 0.050. Why? Purinergic P2X Receptor Antagonists. 1. 2017. 32. 0.050. Why? ... Nuclear Receptor Subfamily 1, Group F, Member 3. 1. 2012. 106. 0.130. Why? ... NK Cell Lectin-Like Receptor Subfamily B. 1. 2014. 71. 0.160. Why? ...
... new potent adenosine A2 receptor antagonists. Eur J Med Chem 28(7-8):569-576. https://doi.org/10.1016/0223-5234(93)90087-U ... and biodistribution of a new potent and selective ligand for in vivo imaging of the adenosine A2A receptor system using ... pyrimidines as inhibitors of receptor tyrosine kinases (RTK). Helv Chim Acta 87(4):956-975. https://doi.org/10.1002/hlca. ...
... completely reversed by a specific adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), but not affected ... by an adenosine A1 receptor antagonist, 8-cyclopentyl-dipropylxanthine. Neither ADA nor DMPX affected leukocyte accumulation in ... Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation.. B N ... Methotrexate, a folate antagonist, is a potent antiinflammatory agent when used weekly in low concentrations. We examined the ...
Activation of nucleotide receptors with extracellular ATP and nucleotide analogues increased ... Regulation of plasma membrane ion transport by endogenous purinergic receptors was assessed in a distal renal (A6) cell line. ... Neither the change in [Ca2+]i nor the stimulation of cotransport was abolished by the adenosine receptor antagonist 8-{4-[N-(2- ... In contrast to the adenosine A2 receptor agonist 5-N-ethylcarboxamidoadenosine, nucleotide analogues had no discernible effect ...
  • In the case of adenosine the pharmacophore is an agonist. (patentgenius.com)
  • Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. (ovid.com)
  • Interestingly, an in vivo model of smooth muscle cell proliferation revealed that an A2 receptor agonist, 2-octynyladenosine, inhibited neointima formation ( 8 ). (pnas.org)
  • A stable adenosine A1 and A2 receptor agonist. (curehunter.com)
  • A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease. (harvard.edu)
  • In contrast to the adenosine A2 receptor agonist 5'-N-ethylcarboxamidoadenosine, nucleotide analogues had no discernible effect on cytosolic adenosine 3',5'-cyclic monophosphate levels or adenylyl cyclase activity. (rti.org)
  • In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. (aspetjournals.org)
  • However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. (aspetjournals.org)
  • The researchers' hypothesis is the foundation of a new study to determine the effects of intracerebroventricular injection of caffeine and the adenosine A1 and A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on treadmill run time to fatigue in rats. (innovations-report.com)
  • Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of α-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist. (ijbs.com)
  • The receptors showed homogeneaus affinities for antagonists but two affinity states for the agonist (-)-epinephrine, which were modulated by guanine nucleotides. (uni-wuerzburg.de)
  • It is concluded that agonist-specific thennodynamic characteristics of ligand binding to a2-receptors of human platelets can only be investigated by regarding differences between high and low affinity agonist binding. (uni-wuerzburg.de)
  • OC differentiation was studied as TRAP+ multinucleated cells following M-CSF/RANKL stimulation of either primary murine bone marrow cells or the murine macrophage line, RAW264.7, in presence/absence of the A(2A)R agonist CGS21680, the A(2A)R antagonist ZM241385, PKA activators (8-Cl-cAMP 100 nM, 6-Bnz-cAMP) and the PKA inhibitor (PKI). (nih.gov)
  • This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. (bvsalud.org)
  • adenosine-5′-diphosphate (ADP), uridine-5′-triphosphate (UTP) and MRS2768, a selective P2Y2 agonist, were applied cumulatively, while adenosine-5′-triphosphate (ATP) and αβ-methylene-ATP (αβ-meATP) response curves were generated from single concentrations per tissue segment. (nottingham.ac.uk)
  • Adenosine (general agonist), NECA (A2Aand A2B receptor agonist) and CGS-21380(A2Aselective agonist), were used in absence and presence of A2A receptors- selective antagonist, ZM-243185, in naive and morphine-dependent rats. (phypha.ir)
  • MRE3008F20 is a highly potent and selective antagonist of adenosine A3 receptor (AA3R) , inhibiting agonist-induced cAMP elevation in resting T lymphocytes with an IC 50 of 5 nM. (medchemexpress.com)
  • Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y1 Receptor. (funcmols.com)
  • The A2A adenosine receptor-selective agonist but not the non-selective A2 receptor agonist, NECA, attenuated ischaemia- and reperfusion-induced stunning. (cf.ac.uk)
  • Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. (ovid.com)
  • Stably transfected cell lines bound a variety of adenosine agonists and antagonists with affinities characteristic of a brain adenosine A2a receptor. (garvan.org.au)
  • The binding of agonists and antagonists to a2-adrenergic receptors of human platelets was studied. (uni-wuerzburg.de)
  • Evidence for the involvement of A1 (inhibitory) and A2 (stimulatory) adenosine receptors in regulating cell growth of these tumor cells was obtained through plating efficiency studies based on the relative potency of adenosine agonists and antagonists. (nus.edu.sg)
  • The distinction between receptor-binding sites for agonists and antagonists underpins the pharmacological differences between these two classes of ligands. (pianolarge.cf)
  • Molecular Recognition of Agonists and Antagonists by the Nucleotide-Activated G Protein-Coupled P2Y2 Receptor. (funcmols.com)
  • Thus, although using the hypoxia→adenosine→A2AR pathway inhibitors may improve antitumor immunity, the recruitment of this pathway by selective drugs is expected to attenuate the autoimmune tissue damage. (pnas.org)
  • Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes. (semanticscholar.org)
  • From previous researches, crystallography for fragment-based screening has been successfully used to discover inhibitors, especially some difficult targets such as b-secretase[5], as well as inhibitors of a wide range of other enzymes: hPNMT, Phosphodiesterase 4A, Hsp90, Bromodomain, Adenosine A2 receptor, etc. (wordpress.com)
  • Antagonists/enzyme inhibitors were applied prior to U46619 addition. (nottingham.ac.uk)
  • Anticoagulants can be further divided into direct factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, and heparin. (teletype.in)
  • Anti-platelet agents (such as aspirin, ADP receptor antagonists, and GPIIb/IIIa antagonists), phosphodiesterase inhibitors and anti-coagulants are major part of the current treatment towards treating ischemic diseases. (eurekaselect.com)
  • The use of antagonists, including caffeine, or targeting the A2 receptors by siRNA pretreatment of T cells improved the inhibition of tumor growth, destruction of metastases, and prevention of neovascularization by antitumor T cells. (pnas.org)
  • We propose to target the hypoxia→adenosine→A2AR pathway as a cancer immunotherapy strategy to prevent the inhibition of antitumor T cells in the tumor microenvironment. (pnas.org)
  • Inhibition of rat ventricular automaticity by adenosine. (semanticscholar.org)
  • After the secretion, 5-HT increases the effects of prothrombotic agents by its binding with 5-HT2 receptors Thromboregulation is also in charge of regulating the process of clot elimination, called primary hemostasis inhibition. (wikipedia.org)
  • This may be now possible because of the recent demonstration that genetic deletion of immunosuppressive A2A and A2B adenosine receptors (A2AR and A2BR) or their pharmacological inactivation can prevent the inhibition of anti-tumor T cells by the hypoxic tumor microenvironment and as a result facilitate full tumor rejection [Ohta A, Gorelik E, Prasad SJ et al (2006) Proc Natl Acad Sci USA 103(35):13132-3137]. (pubmedcentralcanada.ca)
  • Monoamine oxidase B inhibition and neuroprotection: studies on selective adenosine A2A receptor antagonists. (harvard.edu)
  • Thus, 1S,3R-ACPD was determined to activate distinct mGluRs in the striatum that mediate either inhibition or activation of cAMP accumulation, with the latter effect being dependent on the activation of adenosine A2 receptors. (aspetjournals.org)
  • Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. (drugbank.ca)
  • Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension. (ahajournals.org)
  • AZD4635 is in Phase 1 clinical trial with AstraZeneca, to block the adenosine A 2A receptor and immune checkpoint inhibition via PDL1, CTLA4 and enhance the activity of CD73 inhibition. (guidetopharmacology.org)
  • This mechanism is distinct from PDE and adenosine receptor inhibition. (statpearls.com)
  • A(2A)R activation inhibits OC differentiation and regulates bone turnover via PKA-dependent inhibition of NFκB nuclear translocation, suggesting a mechanism by which adenosine could target bone destruction in inflammatory diseases like rheumatoid arthritis. (nih.gov)
  • Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
  • CONCLUSION: Adenosine A2AR antagonists improve 6-OHDA-motor deficit and this effect seems to be mediated by the inhibition of A2A presynaptic receptors in substantia nigra pars compacta. (bvsalud.org)
  • In A431 cells adenosine evoked a biphasic response in which a low concentration (~10 μM) produced inhibition of colony formation but at higher concentrations (up to 100 μM) this inhibition was progressively reversed. (nus.edu.sg)
  • This PET study was conducted to investigate the receptor occupancy of 11 C-SCH442416 in the human brain and to determine plasma concentrations and dose of preladenant which result in inhibition of 11 C-SCH442416 binding to adenosine 2A receptors. (openmedscience.com)
  • Receptor knockouts or pharmacological inhibition in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1-phosphate pathways did not individually alter naive T cell migration. (ox.ac.uk)
  • Antagonist inhibition curves were steep and best described by a one-site binding model. (kzeng.info)
  • The mechanisms of the cardiovascular effects of caffeine include the blocking of adenosine receptors and the inhibition of phosphodiesterases. (kzeng.info)
  • The role of purinergic P2Y12 and P2Y13 receptors in ADPβS-induced inhibition of the cardioaccelerator sympathetic drive in pithed rats. (funcmols.com)
  • Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia) did not differ between A 2A receptor knock-out and wild-type littermates. (jneurosci.org)
  • A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. (aspetjournals.org)
  • However, A2b and A3 receptors are relatively less active than A1 and A2a receptors under normal physiological conditions. (innovations-report.com)
  • 9-13 Movement of the hormone-occupied receptor is not required subsequent to dimerization, and consistent with this, activated receptors appear to be aggregated and essentially immobile at physiological temperature (see section E, chapter 4). (springer.com)
  • The adenylate cyclase-coupled vasopressin V2-receptor is highly laterally mobile in membranes of LLC-PK, renal epithelial cells at physiological temperature. (springer.com)
  • 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-a physiological or pathophysiological agent? (eurekaselect.com)
  • Adenosine mediates many physiological functions via activation of extracellular receptors. (nus.edu.sg)
  • Introduction:Adenosine as a potent vasodilator has physiological role in regulation of regional cerebral blood flow (rCBF). (phypha.ir)
  • Under normal physiological conditions, adenosine is present in sufficient concentrations to activate A 1 and A 2a receptors. (kzeng.info)
  • Previous work showed that adenosine A(2A) antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. (nih.gov)
  • The present work used a T-maze choice procedure to assess the effects of adenosine A(2A) and A(1) antagonism. (nih.gov)
  • Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: studies with a mouse model of parkinsonian tremor. (harvard.edu)
  • It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations [A31642]. (drugbank.ca)
  • [6] [7] This antagonism of the adenosine receptors, specifically A1 receptors, is responsible for some of the side effects of theophylline like seizures and cardiac arrhythmias. (statpearls.com)
  • The main mechanism of action of theophylline is that of adenosine receptor antagonism . (chemeurope.com)
  • Distinct Signaling Patterns of Allosteric Antagonism at the P2Y1 Receptor. (funcmols.com)
  • Indeed, hypoxic cancerous tissues may be protected by the same hypoxia→adenosine→A2AR pathway that was recently shown to be critical and nonredundant in preventing excessive damage of normal tissues by overactive immune cells in vivo ( 18 ). (pnas.org)
  • It is well established that some areas of solid tumors often have transient or chronic hypoxia ( 19 , 20 ), which is conducive to extracellular adenosine accumulation ( 21 ). (pnas.org)
  • First, adenosine levels markedly increase in response to cerebral ischemia and hypoxia as ATP breakdown dramatically increases the formation of adenosine. (jneurosci.org)
  • Interplay of hypoxia and A2B adenosine receptors in tissue protection. (semanticscholar.org)
  • A2B adenosine receptor dampens hypoxia-induced vascular leak. (semanticscholar.org)
  • Extracellular adenosine has been widely implicated in adaptive responses to hypoxia. (rupress.org)
  • Guided by previous work indicating that hypoxia-induced vascular leakage is, at least in part, controlled by adenosine, we generated mice with a targeted disruption of the third coding exon of Cd73 to test the hypothesis that CD73-generated extracellular adenosine functions in an innate protective pathway for hypoxia-induced vascular leakage. (rupress.org)
  • Vascular leakage secondary to hypoxia was reversed in part by adenosine receptor agonists or reconstitution with soluble 5′-nucleotidase. (rupress.org)
  • Previous studies indicated that extracellular nucleotide metabolites, predominantly adenosine, may trigger an endogenous protective mechanism during hypoxia and ischemia ( 12 - 15 ). (rupress.org)
  • Adenosine is produced in response to trauma, ischemia, and hypoxia and plays an important role in preventing excessive tissue damage. (ptglab.com)
  • Because adenosine production increases in hypoxia, the issue of a role of the nucleoside in the renal injury following ischemia reperfusion has been studied extensively. (springer.com)
  • Thus, a stimulatory effect of adenosine was seen in the presence ofXAC, whereas an inhibitory effect was unmasked by NBTI. (uni-wuerzburg.de)
  • Babich V, Vadnagara K, Di Sole F (2015) Dual effect of adenosine a1 receptor activation on renal O2 consumption. (springer.com)
  • Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 report by DelveInsight offers comprehensive insights of the pipeline under development therapeutics scenario and growth prospects across Adenosine A2 Receptor Antagonist development. (bioportfolio.com)
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (nih.gov)
  • We found that adenosine deaminase abolished 1S,3R-ACPD-stimulated cAMP accumulation whereas the adenosine uptake blocker dipyridamole enhanced this response. (jneurosci.org)
  • The methotrexate-mediated reduction in leukocyte accumulation was partially reversed by injection of adenosine deaminase (ADA) into the air pouch, completely reversed by a specific adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), but not affected by an adenosine A1 receptor antagonist, 8-cyclopentyl-dipropylxanthine. (jci.org)
  • Sfib were stimulated with 10 ng/ml TNF-α and pretreated for 2 hours with medium or MTX at varying doses (0, 0.01, 0.1, 1, 10 μM) in the presence or absence of adenosine deaminase, DPCPX (adenosine A1 receptor antagonist) or DMPX (adenosine A2 receptor antagonist). (biomedcentral.com)
  • Adenosine deaminase reversed the effects of MTX as did addition of DMPX but not DPCPX 1 hour prior to MTX. (biomedcentral.com)
  • Both receptors mediate phospholipase C stimulation causing an increase of intracellular levels of inositol 1,4,5-triphosphate and diacylglycerol. (wikipedia.org)
  • This kinase inhibits Gαq-phospholipase C-inositol 1,4,5-triphosphate signaling and the mobilization of calcium inside the cell for thromboxane A2. (wikipedia.org)
  • In addition, platelets with the Q43P β1-tubulin variant had reduced adenosine triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced aggregation and collagen adhesion. (bloodjournal.org)
  • The retinal blood flow is regulated by the tone of resistance arterioles, which is influenced by purinergic compounds such as adenosine and adenosine 5′-triphosphate (ATP) released from the retinal tissue. (