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.
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.
Compounds with a BENZENE fused to IMIDAZOLES.
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.
Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
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.

Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. (1/50)

1. Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A1, A2A and A3 adenosine receptors in this phenomenon. 2. The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity. 3. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nm), completely prevented the protective effect of preconditioning. The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phe nol (ZM 241385, 100 nm) did not modify the magnitude of fepsp recovery compared to control slices. The selective A3 adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nm) significantly improved the recovery of fepsps after 7 min of ischemia. 4. Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A1 receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A2A receptors are not involved in this phenomenon, whereas A3 receptor activation is harmful to ischemic preconditioning.  (+info)

Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. (2/50)

Recent studies demonstrated that resveratrol, a grape-derived polyphenolic phytoalexin, provides pharmacological preconditioning (PC) of the heart through a NO-dependent mechanism. Because adenosine receptors play a role in PC, we examined whether they play any role in resveratrol PC. Rats were randomly assigned to groups perfused for 15 min with 1) Krebs-Henseleit bicarbonate buffer (KHB) only; 2) KHB containing 10 microM resveratrol; 3) 10 microM resveratrol + 1 microM 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A(1) receptor blocker); 4) 10 microM resveratrol + 1 microM 8-(3-chlorostyryl)caffeine (CSC; adenosine A(2a) receptor blocker); 5) 10 microM resveratrol + 1 microM 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5- dicarboxylate (MRS-1191; adenosine A(3) receptor blocker); or 6) 10 microM resveratrol + 3 microM 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride [LY-294002, phosphatidylinositol (PI)3-kinase inhibitor], and groups perfused with adenosine receptor blockers alone. Hearts were then subjected to 30-min ischemia followed by 2-h reperfusion. The results demonstrated significant cardioprotection with resveratrol evidenced by improved ventricular recovery and reduced infarct size and cardiomyocyte apoptosis. CPT and MRS 1191, but not CSC, abrogated the cardioprotective abilities of resveratrol, suggesting a role of adenosine A(1) and A(3) receptors in resveratrol PC. Resveratrol induced expression of Bcl-2 and caused its phosphorylation along with phosphorylation of cAMP response element-binding protein (CREB), Akt, and Bad. CPT blocked phosphorylation of Akt and Bad without affecting CREB, whereas MRS 1191 blocked phosphorylation of all compounds, including CREB. LY-294002 partially blocked the cardioprotective abilities of resveratrol. The results indicate that resveratrol preconditions the heart through activation of adenosine A(1) and A(3) receptors, the former transmitting a survival signal through PI3-kinase-Akt-Bcl-2 signaling pathway and the latter protecting the heart through a CREB-dependent Bcl-2 pathway in addition to an Akt-Bcl-2 pathway.  (+info)

Activation of A3 adenosine receptors attenuates lung injury after in vivo reperfusion. (3/50)

BACKGROUND: A3 adenosine receptor (AR) activation worsens or protects against renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the current study were to examine in an in vivo model the effect of A3AR activation on IR lung injury and investigate the mechanism by which it exerts its effect. METHODS: The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A3 receptor agonist IB-MECA (300 microg/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. RESULTS: IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52 +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester. CONCLUSIONS: In the feline lung, the A3AR agonist IB-MECA confers a powerful protection against IR lung injury. This effect is mediated by a nitric oxide synthase-independent pathway and involves opening of adenosine triphosphate-sensitive potassium channels. Therefore, selective activation of A3AR may be an effective means of protecting the reperfused lung.  (+info)

A3 adenosine receptor activation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase 1/2 phosphorylation in A375 human melanoma cells. (4/50)

Adenosine exerts its effects through four subtypes of G-protein-coupled receptors: A(1), A(2A), A(2B), and A(3). Stimulation of the human A(3) receptor has been suggested to influence cell death and proliferation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt and the Raf/mitogen-activated protein kinase (MAPK/ERK) kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways have central roles in the regulation of cell survival and proliferation. Due to their importance, the cross-talk between these two pathways has been investigated. Here, we show that the A(3) adenosine receptor agonist Cl-IB-MECA stimulates PI3K-dependent phosphorylation of Akt leading to the reduction of basal levels of ERK1/2 phosphorylation, which in turn inhibits cell proliferation. The response to Cl-IB-MECA was not blocked by A(1), A(2A), or A(2B) receptor antagonists, although it was abolished by A(3) receptor antagonists. Furthermore, the response to Cl-IB-MECA was generated at the cell surface, since the inhibition of A(3) receptor expression, by using small interfering RNA, abolished agonist effects. Using A375 cells, we show that A(3) adenosine receptor stimulation results in PI3K-dependent phosphorylation of Akt, leading to the reduction of basal levels of ERK1/2 phosphorylation, which in turn inhibits cell proliferation.  (+info)

Resveratrol-mediated activation of cAMP response element-binding protein through adenosine A3 receptor by Akt-dependent and -independent pathways. (5/50)

A recent study documented a role of adenosine A(3)-Akt-cAMP response element-binding protein (CREB) survival signaling in resveratrol preconditioning of the heart. In this study, we demonstrate that resveratrol-mediated CREB activation can also occur through an Akt-independent pathway. Isolated rat hearts were perfused for 15 min with Krebs-Henseleit bicarbonate (KHB) buffer containing resveratrol in the absence or presence of adenosine A(3) receptor blocker MRS-1191 [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5 -dicar-boxylate], phosphatidylinositol 3 (PI3)-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], mitogen-activated extracellular signal-regulated protein kinase inhibitor PD098059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one], or a combination of LY294002 and PD098059. All hearts were subsequently subjected to 30-min ischemia followed by 2-h reperfusion. Cardioprotection was examined by determining infarct size, cardiomyocyte apoptosis, and ventricular recovery. Resveratrol phosphorylated both Akt and CREB that was blocked by MRS-1191, which also abolished cardioprotective abilities of resveratrol. LY294002 completely inhibited Akt phosphorylation but partially blocked the phosphorylation of CREB. Inhibition of PI3-kinase also partially blocked resveratrol's ability to precondition the heart. PD098059 partially blocked the phosphorylation of CREB and resveratrol-mediated cardioprotection. Preperfusing the hearts with LY294002 and PD098059 together completely abolished the phosphorylation of CREB, simultaneously inhibiting resveratrol-mediated cardioprotection. The results indicate that resveratrol preconditions the hearts through adenosine A(3) receptor signaling that triggers the phosphorylation of CREB through both Akt-dependent and -independent pathways, leading to cardioprotection.  (+info)

Phosphatidylinositol 3-kinase and ERK1/2 are not involved in adenosine A1, A2A or A3 receptor-mediated preconditioning in rat ventricle strips. (6/50)

Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (PKB; also known as Akt) are important antiapoptotic signalling pathways which have recently been implicated in cardioprotection. However, at present the involvement of ERK1/2 and PI3-kinase/PKB in adenosine receptor-mediated cardioprotection is poorly understood. In this study we used isolated rat right ventricular strips, contracted by electrical-field stimulation, in order to investigate the role of ERK1/2 and PI3-kinase/PKB in adenosine receptor-induced cardioprotection. Ventricle strips were pretreated for 2 min with the agonists adenosine (non-selective), CPA (A1 selective), CGS 21680 (A2A selective) and Cl-IB-MECA (A3 selective) before 30 min hypoxia followed by 30 min reoxygenation. Each agonist significantly improved posthypoxic percentage contraction recovery compared to control strips. Similarly hypoxic preconditioning (10 min hypoxia followed by 20 min reoxygenation) significantly improved posthypoxic percentage contraction recovery compared to non-preconditioned strips. The selective adenosine receptor antagonists DPCPX (A1), ZM 241385 (A2A) and MRS 1220 (A3) attenuated cardioprotection induced by CPA, CGS 21680 and Cl-IB-MECA, respectively. Pre-incubation (30 min) of ventricle strips with the MEK1 inhibitor PD 98059 (50 microM) or the PI3-kinase inhibitor wortmannin (100 nM) significantly reduced posthypoxic percentage contraction recovery induced by hypoxic preconditioning. In contrast, PD 98059 and wortmannin had no significant effect on cardioprotection induced by CPA, Cl-IB-MECA or CGS 21680. Overall these data indicate that although selective A1, A2A and A3 adenosine receptor agonists induce preconditioning in rat right ventricular strips the effects are independent of ERK1/2- and PI3-kinase-dependent pathways. In contrast ERK1/2 and PI3-kinase-dependent pathways do appear to be involved in early hypoxic preconditioning.  (+info)

"Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists. (7/50)

The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N(6)-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K(i) value of 0.66 microM. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N(6)-cyclohexyladenine (12), 2-(phenylamino)-N(6)-cycloheptyladenine (19), and 2-phenylamino-N(6)-endo-norbornyladenine (21) as potent A(3) AR ligands with K(i) values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (>200-fold) was 2-(phenyloxy)-N(6)-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy > or = amino > thio. Selected derivatives, including reversine (K(B) value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N(6) position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation.  (+info)

The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure. (8/50)

PURPOSE: Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. METHODS: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. RESULTS: Adenosine triggered A3AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 +/- 11 nM, p < 0.01) and by another A3AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 +/- 0.8 mmHg at 25-microM droplet concentration (n = 10, p < 0.005). CONCLUSIONS: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.  (+info)

PURPOSETo test whether blocking the Na+/H+ antiport reduces intraocular pressure (IOP) in the mouse.METHODSThe electrophysiologic approach (the servo-null micropipette system, SNMS) that had been adapted for continuously monitoring IOP in the mouse was used in a study of the effects of a series of transport inhibitors.RESULTSTopical application of three direct blockers of Na+/H+ exchangers produced comparable reductions in mouse IOP: dimethylamiloride (DMA, -5.0 +/- 0.7 mm Hg), ethylisopropylamiloride (EIPA, -4.1 +/- 1.0), and BIIB723 (-4.9 +/- 1.7 mm Hg). These effects were mediated locally, not systemically, because adding DMA to one eye had no effect on IOP in the contralateral eye. In contrast to the actions of selective inhibitors of Na+/H+ exchange, neither the low-potency inhibitor amiloride nor the inhibitor of Na+-K+-2Cl- cotransport bumetanide by itself was effective. Dorzolamide, which slows delivery of H+ and HCO3- to Na+/H+ and Cl-/HCO3- antiports, also reduced IOP by 2.9 +/- 0.6 mm ...
So this weekend I bid goodbye to another Sac-Con. Le sigh, if only it was more than a one day con... Wait, what did you say? Its GONNA BE!?? Thats frikkin right! From now on, Sac Con (henceforth to be referred to as SUPER Sac-Con) is gonna be a weekend long event! Boy howdy! I guess the reality of WonderCon never returning to the bay is finally sinking in, and a lot of the smaller cons are revving up their game, trying to be the next big contender. Just a week prior to Fanime was a lil show called Big Wow Con, which if youre native to the bay area, you might remember as formerly being referred to as Super Con ...
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The enzyme is most active with L-methionine. It participates in the L-methionine salvage pathway from S-methyl-5-thioadenosine, a by-product of polyamine biosynthesis. T
The Majestic Rollerball Pen offers pen aficionados distinctive style and flair in a collectors grade pen. Its regal profile is accented with brilliant Black Titanium plating and the body is crafted from select Cocobolo
Catalyzes the reversible phosphorylation of S-methyl-5-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.
SWISS-MODEL Repository entry for C4YQD9 (MTAP_CANAW), S-methyl-5-thioadenosine phosphorylase. Candida albicans (strain WO-1) (Yeast)
By: Chris Niles Armstead Maupin meets Carl Hiaasen in a brilliant black comedy that traces the paths of disparate characters floating through New York, about to collide in a treacherous story that will make you think twice about ever answering a classified ad. ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
Heres the really interesting part. People like you guys, who have been keeping up with this the whole way through, youll already know that its a superhero story. However, people are getting BAAU Down 12 and seeing Brilliant Black Starres for the first time will be totally blind sided. The super hero aspect of the story is more like a twist at the end of the chapter as opposed to a running theme, so Im sure it will catch readers off guard. Im also relatively certain that Brilliant Black Starres is gonna be this huge, runaway major success, so being the first appearance of the characters will turn BAAU Down 12 into a huge collectors item on par with Action Comics #1. Im totally serious about this. So when you stop by this Fanime, dont just get one, get a few! Positively guaranteed to skyrocket in value! this could be your childs college fund! Not even kidding ...
This is a pretty good hit rate. Generally virtual screening campaigns are lucky to have a hit rate of a few percent. Curiously, the authors also found a similarly high hit rate during a past VS campaign against the well-known β2 adrenergic receptor. What could be responsible for this high hit rate against GPCRs? The reasons are interesting. One reason could be that GPCRs are very well adapted to bind small molecules in compact pockets, enclosing them and forming many kinds of productive interactions. But more intriguingly, as the authors have noted earlier, there is biogenic bias in favor of certain target-specific chemotypes in commercial libraries that are screened, both during VS as well as HTS. This in turn reflects the biases of medicinal chemists in picking and synthesizing certain kinds of chemotypes based on the importance of drug targets and past successes in hitting these targets. GPCRs clearly are enormously important, and GPCR-friendly ligand chemotypes thus constitute a large ...
364168652 - EP 2081946 B1 20120530 - ADENOSINE DERIVATIVES FOR THE TREATMENT OF PAIN - [origin: WO2008000745A2] Compounds of formula (I) below are disclosed. Their use as medicaments is described, in particular for the treatment of pain or inflammation. In said Fomula, when X=Y=Z=OH, R SUB 1 /SUB is OCH SUB 2 /SUB CF SUB 2 /SUB CF SUB 3 /SUB , phenoxy (substituted with 3-(4- trifluoromethylphenyl), 3,4-dichloro, (3-trifluoromethyl,4-fluoro), (3-trifluoromethyl,4- chloro), (3-chloro, 4-cyano), or 3,5-bis(trifluoromethyl)), l-piperazinyl(4-(3,4- dichlorophenyl)), phenyl (substituted with 3,4-dichloro, 3,5-difluoro, 3,5- bis(trifluoromethyl) or 3,4,5-trifluoro) or 2-benzofuranyl; or when X=Y=OH and Z=OMe, R SUB 1 /SUB is OCH SUB 3 /SUB , OCH SUB 2 /SUB CHF SUB 2 /SUB , OCH SUB 2 /SUB cyclopentyl, O-(2,5- difluorophenyl) or (S)-sec-butylamino; or when X=H and Y=Z=OH, R SUB 1 /SUB is n-hexylamino or cyclopentylamino; or when (IV) X=Z=OH and Y=H, R SUB 1 /SUB is cyclopentylamino;or a pharmaceutically
WASPADAI 50 JENIS ZAT PEWARNA DAN ZAT ADITIF DALAM MAKANAN ANAK ANDA COLOUR Artificial colours Allura red AC 129 Amaranth 123 Azorubine, carmoisine 122 Brilliant Black BN 151 Brilliant Blue FCF133 Brown HT, chocolate brown 155 Erythrosine 127 Green S, food green, acid brilliant green 142 Indigotine, indigo carmine 132 Ponceau, brilliant scarlet 4R…
He has done it again. Alexander Von Meilenwald has put out another brilliant Black metal opus. I am now fully convinced that this man is a musical genius. I know reviewers need to maintain a sense of objectivity, but we also need to recognize brilliant music whenever it slaps us in the face and have the balls to spread the word. And well, this is us fucking wreckingball ...
MRS-4200 Satin Hot Rod Black is a 2K acrylic urethane coating developed for restoration work, coating frames, engine compartments, exterior panels and other surfaces that a black satin finish is required. This product mixes 4:1 with either MRS-4205 Regular activator or MRS-4210 Slow Activator. MRS-4200 Satin Hot Rod Black has excellent adhesion and chemical resistance. Formulated for long term durability. Available in quarts and gallons. ...
مقدمه: گلوتامیک‌اسید یکی از مهم‌ترین آمینواسیدها از نظر کاربردهای صنعتی و تجاری است و تولید میکروبی آن از برخی باکتری‌ها گزارش شده است. با توجه به نقش باکتری‌های پروبیوتیک در ارتقای سلامتی انسان و تقاضای روزافزون کاربرد آنها در صنایع غذایی، در پژوهش حاضر تولید آمینواسیدهای گلوتامیک‌اسید و فولیک‌اسید با استفاده از باکتری‌های پروبیوتیک (بیفیدوباکتریوم، بیفیدوباکتریوم بیفیدوم و اسپرولاکتوباسیلوس) بررسی شد. مواد و روش‏‏ها: چند محیط اختصاصی و محیط MRS آگار برای کشت سویه‌های پروبیوتیک مدنظر استفاده شدند. گلوتامیک‌اسید موجود در ریزموجودات با
Growing evidence suggests functional interaction between CFTR and P2YR. P2Y2R can regulate CFTR activity in different systems (Paradiso et al., 2001; Marcet et al., 2003). Here, we extend these findings by showing that CFTR modulates the P2Y1R signaling pathway. We report that CHO cells express, in addition to P2Y2R (Marcet et al., 2003), the P2Y1R subtype, which does not regulate CFTR activity in CHO-BQ1 cells. Moreover, we show that, in CHO cells, the expression of the recombinant CFTR (CHO-BQ1), but not the expression of the vector alone (CHO-KNUT), causes an apparent switch in the G-protein-coupling of P2Y1R from a Gq/11- to Gi/o-type. This change in G-protein selectivity was specific of P2Y1R since P2Y2R G-protein-coupling remained unaffected by CFTR.. Our findings that the P2Y1R antagonist MRS2179 and the P2Y1R knockdown antisense experiments abolished the ADP-induced Ca2+ response strongly suggest that putative hamster homologous of human P2Y12- or P2Y13-Gi protein-coupled receptors are ...
Home » S-adenosylhomocysteine. s-adenosylhomocysteine (Science: chemical) 5-s-(3-amino-3-carboxypropyl)-5-thioadenosine. Formed from s-adenosylmethionine after transmethylation reactions. Chemical name: L-Homocysteine, S-(5-deoxyadenosin-5-yl)- ...
Adenosine receptors (ARs) trigger signal transduction path ways inside the cellular when turned on by extracellular adenosine. makes an attempt were made to per-silylate the hydroxyl sets of 7 (Scheme 2). Underneath mild circumstances the tertiary hydroxyl group failed to behave while parenting the environment to 95 °C in DMF generated exclusive creation of the ethylcarbamate derivatives dua puluh enam and 4-hydroxyephedrine hydrochloride twenty seven [19] that were deprotected with NH4F in warm methanol to give the wanted 5′-(a) TBDMSCl imidazole DMF rt 18 h seventy four (b) TCA-H2O THF zero 1 l rt two to three h thirty five (c) (i) CDI TETRAHYDROFURAN rt 3 or more h; (ii) MeNH2 rt 16 h 72… Pharmacological Evaluation Pertaining to the apio-type adenosine derivatives 4-16 the binding was measured by us affinities at the hA1 hA2A and FLI-06 supplier hA3AR. The entire results are reported in Table 2 . The capability of each of such adenosine derivatives to contend for radioligand binding at ...
... is known to act as an antagonist of the adenosine A3 receptor. Reversine is a potent inhibitor of the mitotic kinase ...
... is a drug which acts as a potent and selective antagonist for the adenosine A3 receptor, with sub-nanomolar affinity ( ... a new potent and selective adenosine A3 receptor antagonist". European Journal of Pharmacology. 444 (3): 133-41. doi:10.1016/ ... Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and ... A3 Ki=0.2nM) and high selectivity over the other three adenosine receptor subtypes. Simple xanthine derivatives such as ...
... is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM ... Müller CE (2003). "Medicinal chemistry of adenosine A3 receptor ligands". Current Topics in Medicinal Chemistry. 3 (4): 445-62 ... a novel high-affinity antagonist radioligand for human A(3) adenosine receptors". Bioorg Med Chem Lett. 12 (3): 501-3. doi: ... "Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia". Naunyn-Schmiedeberg's Archives of ...
A2B and A3; each is encoded by a different gene. The adenosine receptors are commonly known for their antagonists caffeine and ... The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the ... "Entrez Gene: ADORA2A adenosine A2A receptor". Jacobson KA, Gao ZG (2006). "Adenosine receptors as therapeutic targets". Nature ... Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive ...
... pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry. 46 (7): 1229-41. doi:10.1021/ ... Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ... The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it. This ...
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... "Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ... have a purine structure and bind to some of the same receptors as adenosine. Methylxanthines act as competitive antagonists of ... Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Extracellular ... The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ...
2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". J. Comp ... Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S (December 2005). "A2B adenosine receptor antagonists: recent ... The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human ... "The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". J. Biol. Chem ...
... is an antagonist of all four adenosine receptor subtypes (A1, A2A, A2B, and A3), although with varying potencies. The ... this is a receptor complex with 1 adenosine A1 receptor and 1 dopamine D1 receptor) and the A2A-D2 receptor heterotetramer ( ... this is a receptor complex with 2 adenosine A2A receptors and 2 dopamine D2 receptors). The A2A-D2 receptor heterotetramer has ... a receptor complex composed of 1 adenosine A1 receptor and 1 adenosine A2A receptor) in the axon terminal of glutamate neurons ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular ... N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (5): 1612-6. PMID ... Entrez Gene: ADORA3 adenosine A3 receptor".. *^ Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, ...
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... or rather its adenosine-antagonist behavior). Mandal, Ananya. "Caffeine Pharmacology". Website Medical News. Archived from the ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...
3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists". Journal of Medicinal Chemistry 46 (7 ... 3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: a study on the importance of modifications at the ... 1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): ...
Caffeine acts as an antagonist of adenosine A1 and A2A receptors. Adenosine is a normal neuromodulator that activates adenosine ... There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these ... Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this ... Caffeine also has an excitatory effect on mesocortical cholinergic neurons by acting as an antagonist on adenosine receptors ...
2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system.". J. Comp ... 2002). "1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists.". J. Med. ... "The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia.". J. Biol. ... "Adenosine Receptors: A2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
... such as nicotinic ACh receptors -at micromolar concentrations- or adenosine A3. The exact effects of methoctramine still remain ... Watson N, Barnes PJ, Maclagan J (January 1992). "Actions of methoctramine, a muscarinic M2 receptor antagonist, on muscarinic ... Gallamine triethiodide M2 receptor Muscarinic receptor Acetylcholine Jakubík J, Zimčík P, Randáková A, Fuksová K, El-Fakahany ... Hence, the presence of the antagonist methoctramine provokes an increase of the heart rate. In marked contrast of the above, ...
Wijeyeratne, Yanushi Dullewe; Heptinstall, Stan (October 2011). "Anti-platelet therapy: ADP receptor antagonists". British ... 157 (1): 148.e1-148.e5. doi:10.1016/j.ahj.2008.09.017. PMID 19081411. Drepper, Michael D; Spahr, L; Frossard, JL (2012). " ... P2Y12 receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y12 receptor that leads to ... Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute ...
... leading to an accumulation of adenosine. On the other hand, the adenosine-receptor antagonist caffeine reverses the anti- ... On the other hand, nanomolar concentrations of adenosine activate A1 and A3 receptors, resulting in neutrophilic chemotaxis ... In the airways of patients with asthma, the expression of adenosine receptors is upregulated. Adenosine receptors affect ... the expression of adenosine receptors on the neutrophil, and the affinity of these receptors for adenosine. Micromolar ...
Björklund O, Shang M, Tonazzini I, Daré E, Fredholm BB (2008). "Adenosine A1 and A3 receptors protect astrocytes from hypoxic ... H2-receptor antagonists, like cimetidine (Tagamet), inhibit the signaling pathway that leads to activation of the ATPase. This ... eCollection 2015 Gessi S, Merighi S, Stefanelli A, Fazzi D, Varani K, Borea PA (2013). "A(1) and A(3) adenosine receptors ... Memory has been associated with astrocytes and the alpha3 subunit of adenosine receptor found in hydrogen/Sodium-potassium ...
"Functional studies of the first selective beta 3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Molecular ... 81 (1): 211.e1-7. doi:10.1016/j.urology.2012.09.011. PMID 23200975. Fitzpatrick D, Purves D, Augustine G (2004). "Table 20:2". ... "Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway ... Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2 There is no α1C receptor. There was a subtype known as C, but ...
... adenosine receptor binding affinity (21 μM for A1, 32 μM for A2A, 4.5 μM for A2B, and >100 for μM for A3) is ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in ... Müller, Christa E.; Jacobson, Kenneth A. (2011), Fredholm, Bertil B. (ed.), "Xanthines as Adenosine Receptor Antagonists", ... Studies indicate that, similar to caffeine, simultaneous antagonism of adenosine receptors is responsible for paraxanthine's ...
"Entrez Gene: TACR3 tachykinin receptor 3".. *^ Quartara L, Altamura M (Aug 2006). "Tachykinin receptors antagonists: from ... "Tachykinin Receptors: NK3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... NK3 receptor antagonists are being investigated as treatments for various indications.[7] ... tachykinin receptor activity. • G-protein coupled receptor activity. • signal transducer activity. • protein binding. ...
Lanig H, Utz W, Gmeiner P (April 2001). "Comparative molecular field analysis of dopamine D4 receptor antagonists including 3-[ ... The dopamine receptor D4 is a G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.[5] ... dopamine neurotransmitter receptor activity. • G-protein coupled receptor activity. • protein binding. • dopamine binding. • ... "Dopamine Receptors: D4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ...
MEN-10376 - potent and selective antagonist, 7-amino acid polypeptide chain. CAS# 135306-85-3 ... tachykinin receptor activity. • G-protein coupled receptor activity. • substance K receptor activity. • signal transducer ... "Tachykinin Receptors: NK2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are ...
On the other hand, GHS-R antagonists have anorectic effects and are likely to be useful for the treatment of obesity. ... dopamine receptor type 2 (DRD2),[11] melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT2c receptor).[11] See ... Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth ... 3,3 A3. Start. 27,371,351 bp[2]. End. 27,378,010 bp[2]. RNA expression pattern. ...
... of mixed GHB/GABAB receptor agonists along with a selective GABAB antagonist or selective agonists for the GHB receptor which ... Receptor/signaling modulators. GABA receptor modulators. Glutamate receptor modulators. Glycine receptor modulators. ... The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is a G protein-coupled receptor (GPCR) that ... The function of the GHB receptor appears to be quite different from that of the GABAB receptor. It shares no sequence homology ...
... adrenoceptor antagonist with minimal dopamine D(2) and 5-HT(1A) receptor affinity". Eur. J. Pharmacol. 433 (1): 123-7. doi: ... Receptor[edit]. There are 3 alpha-1 adrenergic receptor subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 ... G-protein coupled receptor activity. • signal transducer activity. • adrenergic receptor activity. • protein binding. • alpha1- ... The alpha-1D adrenergic receptor (α1D adrenoreceptor), also known as ADRA1D, is an alpha-1 adrenergic receptor, and also ...
Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (Jan 1990). "The selective CCK-B receptor antagonist L- ... 7 E3,7 55.86 cM. Start. 105,425,731 bp[2]. End. 105,470,898 bp[2]. ... type B gastrin/cholecystokinin receptor binding. • gastrin receptor activity. • cholecystokinin receptor activity. • peptide ... "Entrez Gene: CCKBR cholecystokinin B receptor".. *^ Altar CA, Boyar WC (Apr 1989). "Brain CCK-B receptors mediate the ...
... antagonist. References[edit]. *^ de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (2000). " ... Main article: Angiotensin II receptor type 2. AT2 receptors are more plentiful in the fetus and neonate. The AT2 receptor ... The angiotensin II receptors, (AGTR1) and (AGTR2), are a class of G protein-coupled receptors with angiotensin II as their ... The AT1 receptor is the best elucidated angiotensin receptor. Location within the body[edit]. The AT1 subtype is found in the ...
transmembrane signaling receptor activity. • Wnt-activated receptor activity. • G-protein coupled receptor activity. ... "Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action". Proc. Natl. Acad. Sci. U.S.A. 94 ... "Frizzled Receptors: FZD5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... Leukotriene-A4 hydrolase), or are the cellular receptors responsible for mediating the cellular responses to the down-stream ... 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 ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14) ... 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] ...
腺苷酸(英语:Adenosine receptor) (A1, A2A, A2B, A3) · P2Y(英语:P2Y receptor) (1(英语:P2RY1), 2(英语:P2RY2), 4(英语:P2RY4), 5(英语:LPAR6), 6(英语: ... GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. British Journal of Pharmacology. January 1994 ... 乙酰胆碱 (M1, M2, M3, M4, M5) · 多巴胺(英语:Dopamine receptor) (D1, D2, D3, D4, D5) · 组织胺(英语:Histamine receptor) (H1, H2, H3, H4) · 褪黑素( ... α1(英语:Alpha-1 adrenergic receptor) (A, B, D) · α2(英语:Alpha-2 adrenergic receptor) (A, B
... the toll-like receptors, the C-type lectin receptors, the NOD-like receptors, and the RIG-I-like receptors. Invariably, the ... and H2 antagonist are useful in a person with risk factors of developing upper gastrointestinal bleeding (UGIB) such as on ... and low production of adenosine triphosphate (ATP), can cause myocardial depression, reducing cardiac contractility and causing ... 29 (1): 185.e1-7. doi:10.1016/j.jcrc.2013.09.031. PMID 24262273.. ...
"Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... 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 ... "EP3-2 receptor mRNA expression is reduced and EP3-6 receptor mRNA expression is increased in gravid human myometrium". Journal ...
D2 receptor antagonists (e.g., domperidone, metoclopramide, risperidone) ... 18 E3,18 55.78 cM. Start. 82,392,496 bp[2]. End. 82,406,777 bp[2]. ... Galanin receptor 1 (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene.[5] ... "Galanin Receptors: GAL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
... drugs which are selective receptor antagonists of CysLTR1 but not CysLTR2.[20][21][22][23] Models of allergic reactions in ... 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 ... Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes# ...
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 ... Paul-Clark, Mark J.; Cao, Thong van; Moradi-Bidhendi, Niloufar; Cooper, Dianne & Gilroy, Derek W. 15-epi-lipoxin A4-mediated ... ADP receptor inhibitor)(如氯吡格雷、普拉格
mineralocorticoid receptor activity. • steroid binding. • G-protein coupled receptor activity. • steroid hormone receptor ... CCL18 has been identified as an endogenous antagonist of the GPER.[16] ... Receptor/signaling modulators. Estrogens and antiestrogens. Androgen receptor modulators. Progesterone receptor modulators. ... G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans ...
Antagonists: AR-A000002. *Beta blockers (e.g., alprenolol, carteolol, isamoltane, oxprenolol, penbutolol, propranolol, ... There is no 5-HT1C receptor, as it was reclassified as the 5-HT2C receptor.[2] For more information, please see the respective ... The 5-HT1 receptors are a subfamily of the 5-HT serotonin receptors that bind to the endogenous neurotransmitter serotonin ( ... 5-HT7 receptor. References[edit]. *^ Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey ...
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) ... "Prostanoid receptors - G protein-coupled receptors - IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org.. ...
... 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+ ... 135 (4): 1383-1391, 1391.e1-5. doi:10.1053/j.gastro.2008.08.045. PMID 18789939.. ... H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux ...
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) ...
NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone). *Opioids (e.g., hydrocodone, morphine, oxycodone, ... "Morphine-induced spinal release of adenosine is reduced in neuropathic rats". Anesthesiology. 95 (6): 1455-9. doi:10.1097/ ... 49 (2): 178-85, 185.e1-4. doi:10.1016/j.annemergmed.2006.07.016. PMID 17098328.. ... The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Local anesthetic drugs ...
... the toll-like receptors, the C-type lectin receptors, the NOD-like receptors, and the RIG-I-like receptors. Invariably, the ... 185.e1-7։ February 2014։ PMID 24262273։ doi:10.1016/j.jcrc.2013.09.031 ,vauthors=. պարամետրը գոյություն չունի (օգնություն) ... and H2 antagonist are useful in a person with risk factors of developing upper gastrointestinal bleeding (UGIB) such as on ... and low production of adenosine triphosphate (ATP), can cause myocardial depression, reducing cardiac contractility and causing ...
... dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while ... increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP).[6] ... μ-opioid receptors. ↑μ-opioid receptors. ↑κ-opioid receptors. ↑μ-opioid receptors. ↑μ-opioid receptors. No change. No change. [ ... The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are ...
PDP2 receptor antagonists have been shown to allergic reactions induced in the airways mice and sheep as well as the airways ... 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 ... Ramatroban, vidupiprant, and Bay U3405 are non-selective (i.e. known to influence other receptors) antagonists of DP2.[9] ...
Use of antagonistsEdit. Selective CB1 agonists may be used to isolate the effects of the receptor from the CB2 receptor, as ... Through its primary action as a Gi coupled receptor, CB1 inhibits production of cyclic adenosine monophosphate (cAMP), ... 4 A5,4 16.28 cM. Start. 33,924,593 bp[2]. End. 33,948,831 bp[2]. ... "Cannabinoid Receptors: CB1". IUPHAR Database of Receptors and ... Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in ...
... receptor promoter: regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway". Endocrinology. 145 (12): ... "Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function". Molecular Psychiatry ... "Corticotropin-releasing Factor Receptors: CRF2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic ... corticotrophin-releasing factor receptor activity. • transmembrane signaling receptor activity. • peptide hormone binding. • ...
Not all GABAA receptors are ethanol sensitive. ... Ethanol also acts as an NMDA antagonist by allosterically inhibiting the ... "Ethanol Blocks Adenosine Uptake via Inhibiting the Nucleoside Transport System in Bronchial Epithelial Cells.". Alcohol Clin ... Accordingly, the opioid receptor antagonist naltrexone reduces ethanol self-administration in animals and is used with modest ... The initial effects of ethanol result primarily from facilitation of GABAA receptors and inhibition of NMDA glutamate receptors ...
D2 receptor antagonists (e.g., domperidone, metoclopramide, risperidone) ... "Neurotensin Receptors: NTS1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Neurotensin receptor 1, also called NTR1, belongs to the large superfamily of G-protein coupled receptors and is considered a ... NTSR1, NTR, Neurotensin receptor 1, neurotensin receptor 1 (high affinity). External IDs. MGI: 97386 HomoloGene: 68261 ...
Antagonists[edit]. *Agouti signalling peptide - nonselective peptide antagonist. In other organisms[edit]. ... 8 E1,8 72.1 cM. Start. 123,407,107 bp[2]. End. 123,410,744 bp[2]. ... melanin-activating peptide receptor, or melanotropin receptor, is a G protein-coupled receptor that binds to a class of ... "Melanocortin Receptors: MC1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
When appropriately modified, they show selectivity toward A1 or A3 receptors, which results in a variety of therapeutic ... Thiazole and thiadiazole analogues have been recently proposed as a novel promising class of adenosine A1 and A3 receptor ... QSAR study on thiazole and thiadiazole analogues as antagonists for the adenosine A1 and A3 receptors Bioorg Med Chem. 2005 Sep ... we carried out a QSAR study on thiazole and thiadiazole analogues as antagonists for adenosine A1 and A3 receptors. To develop ...
... antagonists (1-3) selected from 4-acylamino-6-alkyloxy-2-alkylthiopyrimidines previously investigated by us were modified by ... Three A3 adenosine receptor (AR) antagonists (1-3) selected from 4-acylamino-6-alkyloxy-2-alkylthiopyrimidines previously ... of chiral 4-acetylamino-6-alkyloxy-2-alkylthiopyrimidines acting as antagonists of the human A3 adenosine receptor ... of chiral 4-acetylamino-6-alkyloxy-2-alkylthiopyrimidines acting as antagonists of the human A3 adenosine receptor B. Cosimelli ...
... and Water-Soluble Human A3 Adenosine Receptor Antagonist ... K B value 3 Adenosine Receptor Antagonist CHO cells hA 3 ... A new, highly potent, selective, and water-soluble antagonist of the hA,sub,3,/sub, adenosine receptor was synthesized and ... Adenosine Receptor Antagonist. 2002-07-16T00:00:00Z (GMT) by Anna Maconi Giorgia Pastorin Tatiana Da Ros Giampiero Spalluto ... adenosine receptor First Potent Schild analysis K i 0.01 nM hA 3 receptor Molecular Modeling Investigation pyrimidine ...
... high quality Adenosine receptor antagonist from Hello Bio, a trusted supplier for life science researchers worldwide ... Buy CellAura fluorescent adenosine A3 antagonist [XAC] - an affordable, ... Fluorescent Adenosine A3 receptor Antagonist (A3-633-AN), A3-633-AN ... Conversion of a non-selective adenosine receptor antagonist into A3-selective high affinity fluorescent probes using peptide- ...
... Author:. Jandova, Zuzana. Jespers ... Free-energy calculations for bioisosteric modifications of A3 adenosine receptor antagonists. Please use this identifier to ... Free-Energy Calculations for Bioisosteric Modifications of A3 Adenosine Receptor Antagonists. Int. J. Mol. Sci. 2019, 20, 3499 ... We investigate the thermodynamics of ligand binding to the A3 adenosine receptor subtype, focusing on a recently reported ...
... pyrimidine Nucleus as Adenosine Receptor Antagonists: Shift in Selectivity from A2A to A3 Adenosine Receptors. ... pyrimidine Nucleus as Adenosine Receptor Antagonists: Shift in Selectivity from A2A to A3 Adenosine Receptors. ... 1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for ... 1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for ...
A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The ... Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced ... Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse M ... Adenosine / Plasminogen Activator Inhibitor 1 / Receptors, Purinergic P1 / Oxidative Stress Language: English Journal: Journal ...
... receptor antagonist, KF26777 (2-(4-bromophenyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one dihydrochloride). This ... compound was characterized using N(6)-(4-amino-3-iodobenzyl)adenosine-5-N-methyluronami … ... We investigated the biochemical and pharmacological properties of a new adenosine A(3) ... a new potent and selective adenosine A3 receptor antagonist Eur J Pharmacol. 2002 May 31;444(3):133-41. doi: 10.1016/s0014-2999 ...
antagonist. Details. DB00640. Adenosine. approved, investigational. yes. agonist. Details. DB05511. Piclidenoson. ... Adenosine receptor A3. Details. Name. Adenosine receptor A3. Synonyms. Not Available. Gene Name. ADORA3. Organism. Humans. ... G-protein coupled adenosine receptor activity. Specific Function. Receptor for adenosine. The activity of this receptor is ... Sajjadi FG, Firestein GS: cDNA cloning and sequence analysis of the human A3 adenosine receptor. Biochim Biophys Acta. 1993 Oct ...
A3 adenosine receptor[edit]. Main article: Adenosine A3 receptor. It has been shown in studies to inhibit some specific signal ... Adenosine receptors Receptor. Gene. Mechanism [15]. Effects. Agonists. Antagonists A1 ADORA1. Gi/o → cAMP↑/↓ *Inhibition *↓ ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ...
Nonselective adenosine receptor antagonist (Blocks A1, A2, A3 equally). Mechanism: Nonspecific AChRi -,promotes degrdation of ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b And A3 Adenosine Receptors. ...
... highly selective adenosine A3 receptor (A3AR) agonist with potential antineoplastic activity. ... CF-102 is an orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential ... CF-102 is an orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential ... Antagonist. CAS No.. 163042-96-4. Formula. C18H18ClIN6O4. M. Wt. 544.73079. Solubility. DMSO. ...
Electronic Structure of some A3 Adenosine-Receptor Antagonist--A Structure Activity Relationship (Articles) ... Recent Development in Thrombin Receptor Antagonist as Novel Antithrombotic Agent (Articles). Huan Cui, Weiqiang Tan, Jianshuo ... Efficacy of the H2-receptor antagonist famotidine on chronic spontaneous urticaria in children (Articles) ... GnRH Antagonist Protocol: Is It Optimal for All Patients of Different Ages Undergoing In Vitro Fertilization and Embryo ...
A3 adenosine receptor antagonist,ARK-1/-2/-3 inhibitor. 0. Genes that share compounds with INCENP: view ...
Reversine is known to act as an antagonist of the adenosine A3 receptor. Reversine is a potent inhibitor of the mitotic kinase ...
Nucleoside-derived antagonists to A3 adenosine receptors lower mouse intraocular pressure and act across species. Exp Eye Res ...
Conversion of a non-selective adenosine receptor antagonist into A3-selective high affinity fluorescent probes using peptide- ... Molecular dynamics simulations of the adenosine A2a receptor: structural stability, sampling, and convergence. Journal of ...
e, THP-1 cells pretreated with antagonists targeting adenosine receptors A1, A2a and A3, apyrase or suramin prior to migration ... a, Effect of pretreatment of monocytes with P2Y receptor antagonist suramin (100 μM) on migration to apoptotic cell ... Right, qPCR and agarose gel electrophoresis (inset, inverted image) analysis of P2Y2 receptor mRNA levels in siRNA transfected ... P2Y2 receptor on monocytes and macrophages as a sensor of ATP/UTP released by apoptotic cells ...
10.2 Adenosine A3 receptor (A3AR) antagonists. *10.2.1 Piclidenoson (CF101; Can-Fite Biopharma) ...
... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular ... N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (5): 1612-6. PMID ... Entrez Gene: ADORA3 adenosine A3 receptor".. *^ Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, ...
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... "Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ...
Pharmacokinetics of lj-2698, a potent human a3 adenosine receptor antagonist, in rats ... Double maintenance dose of clopidogrel is associated with reduction in adenosine diphosphate induced aggregation ...
Selective Glucocorticoid Receptor Ligands. Medicinal Chemistry. * Medicinal Chemistry of Adenosine A3 Receptor Ligands. Current ... As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near ... As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near ... Kinin Receptors and Their Antagonists as Novel Therapeutic Agents. Author(s): Yusuf Ozturk. Department of Pharmacology, Faculty ...
Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone ... AAdenosine receptor A1. antagonist. Human. AAdenosine receptor A3. antagonist. Human. ... G-protein coupled adenosine receptor activity. Specific Function. Receptor for adenosine. The activity of this receptor is ... Stella L, de Novellis V, Marabese I, Berrino L, Maione S, Filippelli A, Rossi F: The role of A3 adenosine receptors in central ...
Female C57BL/6 mice were injected with Con A (12 mg/kg, i.v.) to induce liver inflammation (20). Adenosine receptor antagonists ... whereas it has much lower affinity to the A3 adenosine receptor (1). To distinguish roles of A1R and A2AR in liver damage, we ... 3 Abbreviations used in this paper: A2AR, A2A adenosine receptor; ALT, alanine aminotransferase; A1R, A1 adenosine receptor; ... Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and ...
Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors. Current Pharmaceutical Design ... Challenges for Drug Discovery - A Case Study of Urokinase Receptor Inhibition. Combinatorial Chemistry & High Throughput ...
5. U.S. Patent Application 13/371,081, filed February 10, 2012, titled "A3 Adenosine Receptor Agonists And Antagonists" [HHS ... 7. U.S. Provisional Application 62/033,723, filed August 6, 2014, titled "A3 Adenosine Receptor Agonists" [HHS Ref. No. E-210- ... 1. U.S. Patent 8,735,407, issued May 27, 2014, titled "Purine Derivatives As A3 Adenosine Receptor-Selective Agonists" [HHS Ref ... 6. U.S. Provisional Application 61/909,742, filed November 27, 2013, titled "A3 Adenosine Receptor Agonists" [HHS Ref. No. E- ...
... selectively inhibits adenosine A3 receptors (Ki = 3.25 µM) and CYP3A4 catalytic activity (IC50 = 0.148 µM); activates TRPA1 ... acts as a receptor antagonist (beta blocker) or inverse agonist for β1 and β2 receptors but functions as an agonist at the… ... A full agonist of the serotonin 5-HT1A receptor and antagonist of 5-HT2A (Kis = 1 and 49 nM, respectively); also binds to ... An anti-coagulant; differs from (−)-warfarin by being five times less potent as a vitamin K antagonist; has a longer terminal ...
... 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 ...
  • When appropriately modified, they show selectivity toward A1 or A3 receptors, which results in a variety of therapeutic potentialities of these ligands. (nih.gov)
  • Application of datasets by using CODESSA software led to QSAR equations based on three and four descriptors for the adenosine A1 and A3 receptor ligands, respectively. (nih.gov)
  • Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. (units.it)
  • Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
  • A number of selective A3 ligands are available. (wikipedia.org)
  • Also disclosed are conjugates comprising a dendrimer and one or more ligands, which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. (nih.gov)
  • Novel ligands (small molecules) for these receptors are developed using classical synthetic approaches and also by semirational methods based on molecular modeling and template design. (nih.gov)
  • Recent accomplishments include the design and synthesis of the highly potent and selective A3 adenosine receptor agonists and antagonists, using a combination of library screening and optimization of known adenosine receptor ligands. (nih.gov)
  • I am interested in how activation of one of these classes of receptor leads to modification of the response to other receptor classes (cross-talk), as well as how different ligands can provoke different signalling profiles at the same receptor (agonist bias). (nottingham.ac.uk)
  • Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. (nottingham.ac.uk)
  • G protein-coupled receptor list: recommendations for new pairings with cognate ligands. (nottingham.ac.uk)
  • The A 3 receptor is more and more being well-known for its organic roles through the physique, and lots of A 3 receptor ligands have confirmed important in elucidating peripheral and principal pathologies. (stainlessqa.com)
  • Both N-2-isopentenyladenosine IPA and racemic zeatin riboside were shown to be selective human adenosine A3 receptor hA3R ligands with affinities in the high nanomolar range Ki values of 159 and 649 nM, respectively. (duhnnae.com)
  • methods of their production, new intermediate compounds of described methods of production, a pharmaceutical composition containing these compounds, and application of compounds of common formula (I) and their pharmaceutical acceptable salts as ligands of adenosine A3 receptor in treatment of different diseases. (russianpatents.com)
  • Identification of an increasing number of physiological functions mediated by adenosine, and the opening of new adenosine receptor subtypes provides opportunities for therapeutic application of certain ligands (Poulse S.A. and R.J. Quinn Bioorganic and Medicinal Chemistry 6:619, 1998). (russianpatents.com)
  • All the ligands tested along with exogenous adenosine had a significant statistical effect on one ERG component or another. (hi.is)
  • Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. (wikipedia.org)
  • Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. (ovid.com)
  • Our overall goals are to design, chemically synthesize, and characterize pharmacologically new agonists and antagonists for the four subtypes of adenosine receptors (ARs) and eight subtypes of P2Y receptors and to explore their potential for treating human disease conditions. (nih.gov)
  • 0004] This application relates to uses of A.sub.2a adenosine receptor agonists and antagonists to modulate T-cell mediated tolerance to antigenic stimuli. (patents.com)
  • Adenosine receptors: development of selective agonists and antagonists. (wikipathways.org)
  • The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. (drugbank.ca)
  • R1530 is also a mitosis-angiogenesis inhibitor (MAI) that inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, platelet-derived growth factor receptor (PDGFR) beta? (adooq.com)
  • Exposure to bacteria or an A3AR agonist stimulates the formation of these projections and bacterial phagocytosis, whereas an A3AR‐selective antagonist inhibits cytoneme formation. (nottingham.ac.uk)
  • It is known that the interaction with the adenosine A3 receptor inhibits several activities of these cells including the release of TNF-alpha and other potent inflammatory cytokines such as IL-6 and IL-8 and increases the production of IL-10 with anti-inflammatory activity. (unife.it)
  • In the CNS, adenosine inhibits synaptic release of neurotransmitters, and this effect is mediated by receptors And 1 . (russianpatents.com)
  • As a folic acid antagonist, methotrexate inhibits purine and pyrimidine synthesis, resulting in antineoplastic activity at high dose levels. (omicsonline.org)
  • Their theory is based on the fact that adenosine is produced within the body and inhibits neuronal excitability and synapse transmission. (innovations-report.com)
  • Adenosine also inhibits the release of most brain excitatory neurotransmitters, particularly dopamine (DA), and may reduce DA synthesis. (innovations-report.com)
  • 2'-MeCCPA is a potent and highly selective agonist at A1 adenosine receptors (Ki values are 3.3, 9580, 37600 and 1150 nM for human recombinant A1, A2A, A2B and A3 receptors respectively), which acts as a full agonist and inhibits forskolin-stimulated adenylyl cyclase activity in rat cortical membranes with an IC50 value of 13.1 nM. (emmx.com)
  • A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis . (bvsalud.org)
  • In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. (bvsalud.org)
  • Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria . (bvsalud.org)
  • CF-102 is an orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential antineoplastic activity. (adooq.com)
  • Both eyes of OHT or pONT were intravitreally injected with either 2-Cl-IB-MECA, PBS (vehicle) or 1.2 µM 2-Cl-IB-MECA + 1.2 µM MRS 1220 (A3AR antagonist) immediately before surgery. (arvojournals.org)
  • Rats treated with both A3AR agonist and antagonist did not show significant difference from insult alone. (arvojournals.org)
  • The A3‐adenosine receptor (A3AR) has recently emerged as a key regulator of neutrophil behaviour. (nottingham.ac.uk)
  • This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. (elsevier.com)
  • Adenosine A3 receptor (A3AR) antagonists are a novel oral treatment for glaucoma. (acornbio.com)
  • The A3AR subtype is the most recently characterized member of the adenosine receptor family. (acornbio.com)
  • The A3AR holds promise in glaucoma because knockout of the A3AR reduces IOP in the living mouse and A3AR antagonists have been shown to reduce IOP in rodents, rabbits, and both normal and glaucomatous monkey. (acornbio.com)
  • A3AR antagonists physiologically decrease inflow of aqueous humor by inhibiting Cl- channels of the NPE at the aqueous surface. (acornbio.com)
  • It has also been observed that antagonists of A3AR are neuroprotective to oxygen and glucose deprived hippocampal tissue. (acornbio.com)
  • A3AR are present on retinal ganglion cells and antagonists of the A3AR have the potential to be neuroprotective in patients with glaucoma. (acornbio.com)
  • Development of a therapeutic A3AR antagonist has thus far been impeded by the lack of cross-species affinity and specificity. (acornbio.com)
  • Various A3AR antagonists had been identified, yet none exhibited similar levels of specificity and selectivity for both the rodent and human A3AR, precluding nomination as therapeutic candidates. (acornbio.com)
  • ACN-1052 is the first orally bioavailable, potent, selective, and specific A3AR antagonist with single digit nM affinity for both the human and rat A3AR. (acornbio.com)
  • 2013. The selective A3AR antagonist LJ-1888 ameliorates UUO-induced tubulointerstitial fibrosis. (springer.com)
  • Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. (drugbank.ca)
  • A nucleotidase inhibitor and A2a adenosine receptor antagonist inhibited the apoptotic supernatant-induced gene expression, suggesting AMP was metabolized to adenosine by an ecto-5'-nucleotidase expressed on macrophages, to activate the macrophage A2a adenosine receptor. (elifesciences.org)
  • also acts as A3 adenosine receptor antagonist (Ki: 660 nM) or aurora kinases inhibitor (IC50: 400-500 nM for Aurora A/B/C respectively). (axonmedchem.com)
  • 1. A method of enhancing an immune response in a host, comprising administering to the host an A.sub.2a receptor antagonist in combination or alternation with a checkpoint inhibitor. (patents.com)
  • 7. A composition of claim 1 where the Rho-kinase inhibitor is Y 27632 and the adenosine A3 receptor antagonist is a 1,2,4 triazolo(1,5-c)pyrimidine. (patentsencyclopedia.com)
  • An orally available, small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), with potential antineoplastic activity. (blogspot.com)
  • An orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), with potential antineoplastic activity. (blogspot.com)
  • An orally available inhibitor of multiple kinases, including the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), the neurotrophic tyrosine receptor kinase (NTRK) types 1, 2 and 3, the proto-oncogene SRC, and focal adhesion kinase (FAK), with potential antineoplastic activity. (blogspot.com)
  • There are at least two subtypes of adenosine receptors in the heart: A1 and A2. (justia.com)
  • NECA was chosen for the study because caffeine is a nonselective adenosine receptor antagonist, and it is not known which of the four subtypes of adenosine receptors may be involved in an effect of caffeine on fatigue. (innovations-report.com)
  • For two Y1 receptor heterodimer combinations (with the Y4 receptor or β 2-adrenoceptor), agonist and antagonist pharmacology was explained by independent actions on the respective orthosteric binding sites. (aspetjournals.org)
  • Thus, allosteric interactions between Y1 and Y5 receptors modify the pharmacology of the heterodimer, with implications for potential antiobesity agents that target centrally coexpressed Y1 and Y5 receptors to suppress appetite. (aspetjournals.org)
  • I am a medicinal chemist with interests in the structure and pharmacology of receptors and in developing drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
  • Thus, in marked contrast to the β-adrenoceptors, the A1-receptor conforms to the long-held principle of pharmacology that antagonist affinity measurements are constant regardless of the response being measured and the competing agonist used to stimulate that response. (aspetjournals.org)
  • My central area of research concerns the pharmacology and biochemistry of G protein-coupled receptors (in particular, cannabinoid, adenosine and glutamate) in the CNS and peripheral tissues. (nottingham.ac.uk)
  • A3 Adenosine Receptors from Cell Biology to Pharmacology and by John R. Fozard (auth. (stainlessqa.com)
  • This booklet "A3 Adenosine Receptors from telephone Biology to Pharmacology and Therapeutics " files the current country of information of the adenosine A3 receptor. (stainlessqa.com)
  • A3 Adenosine Receptors from mobile Biology to Pharmacology and Therapeutics" is an up to the moment and scientifically very good resource of knowledge, beautiful to simple and medical scientists alike. (stainlessqa.com)
  • Pharmacology of Histamine Receptors provides a precis of the pharmacology of histamine receptors. (stainlessqa.com)
  • In this session the latest research in the field of receptor pharmacology and signal transduction will be presented. (figondmd.nl)
  • The adenosine receptors (or P1 receptors [1] ) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand . (wikipedia.org)
  • The mechanism of physiologically relevant increases in the levels of endogenous adenosine to enable the adenosine-mediated down-regulation of inflammation in hypoxic areas of inflamed tissues is supported by observations of the obstruction of blood perfusion in inflamed tissue ( 13 ). (jimmunol.org)
  • Catecholamine depletion with reserpinisation enhances the responsiveness of the coronary resistance vessels to endogenous adenosine through activation of the A2B adenosine receptor. (edu.au)
  • Adenosine is an endogenous and ubiquitous nucleoside that exerts many biological functions through interaction with 4 distinct subtypes of G protein-coupled receptors divided into A1, A2A, A2B, and A3. (unife.it)
  • Release of endogenous catecholamines and activation of the beta-adrenergic receptors (b-AR) have also been shown to be involved in ischaemic preconditioning. (sun.ac.za)
  • Adenosine is a known component of several biologically active endogenous molecules (ATP, NAD + , nucleic acids). (russianpatents.com)
  • 2004. Adenosine: An endogenous regulator of innate immunity. (springer.com)
  • In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. (iospress.com)
  • We investigate the thermodynamics of ligand binding to the A3 adenosine receptor subtype, focusing on a recently reported series of diarylacetamidopyridine inhibitors via molecular dynamics simulations. (usc.es)
  • In the past most of the anti-inflammatory effects of this nucleoside were thought to be due to the activation of the A2A subtype, however more recently, the involvement of the A3 subtype has been also considered relevant for the outcome of inflammation. (unife.it)
  • Finally, in lymphocytes, activation of A3 receptor subtype would result in a reduction of the accession of killer T cells to tumor cells by exerting an immunosuppressive effect and suggesting a role for antagonists of this receptor as anti-tumoral drugs. (unife.it)
  • The subtype of receptor-A 2 can be subdivided into two subtypes - A 2a and A 2b - which stimulate adenylate cyclase activity. (russianpatents.com)
  • Potent adenosine receptor antagonists that are selective for the A1 receptor subtype. (wikipathways.org)
  • The behavioral activation by caffeine is largely accounted for by the antagonism of tonic activation of the A2A adenosine receptor (A2AR) 3 in the brain ( 1 ). (jimmunol.org)
  • However, Y1/Y5 receptor BiFC dimers, compared with the constituent subtypes, were characterized by reduced potency and efficacy of Y5-selective peptide agonists, the inactivity of Y1-selective antagonists, and a change from surmountable to nonsurmountable antagonism for three unrelated Y5 antagonists. (aspetjournals.org)
  • The main mechanism of action of theophylline is that of adenosine receptor antagonism . (chemeurope.com)
  • The CellAura fluorescent adenosine A 3 antagonist [XAC] ligand was shown to antagonize the activity of the adenosine receptor agonist, NECA, in three separate recombinant CHO cell lines expressing the human A 1 , A 2A or A 3 receptor and a cyclic AMP-responsive secreted placental alkaline phosphatase (SPAP) reporter gene. (hellobio.com)
  • A2AR is a G s protein-coupled receptor, and ligand binding to A2AR increases intracellular cAMP. (jimmunol.org)
  • Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. (nus.edu.sg)
  • Receptors are computer-modeled by homology to GPCRs of known structure, and the models for ligand recognition are tested and refined using site-directed mutagenesis of the receptor proteins. (nih.gov)
  • The antagonist affinity for a given receptor is traditionally considered to be constant, reflecting the chemical nature of the specific ligand-receptor interaction. (aspetjournals.org)
  • It is well known that there is complementarity in shape and electrostatics between a ligand molecule and its receptor protein. (biomedcentral.com)
  • While the electrostatic reaches into the long range, the partial charges also contribute to the molecular recognition in the short range where they are the driving forces of polar interactions (hydrogen bonding and salt bridges) determining the specificity of recognition as well as the coordination of bridging waters between the receptor and ligand. (biomedcentral.com)
  • A(1) adenosine receptor agonists: medicinal chemistry and therapeutic potential. (wikipathways.org)
  • Adenozinski A 3 receptor ( ADORA3 ) je adenozinski receptor . (wikipedia.org)
  • The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it. (wikipedia.org)
  • We hypothesized that cancerous tissues are protected from antitumor T cells because of immunosuppressive signaling via T cell A2A adenosine receptor (A2AR) ( 15 - 17 ) activated by extracellular adenosine produced from hypoxic tumor ( Fig. 1 a ). (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)
  • My current focus is on receptors for purines, encompassing both adenosine receptors and P2 receptors, which are activated by ATP, UTP and other extracellular nucleotides. (nih.gov)
  • Recently, the involvement of extracellular loops of GPCRs have been implicated in the receptor binding of small molecules. (nih.gov)
  • The study shows effects of the nonselective adenosine A(1)/A(2A) receptor antagonist caffeine and the selective A(2A) receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A(2A) receptor density in the rat striatum. (biomedsearch.com)
  • Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. (biomedsearch.com)
  • Caffeine (10 and 20 mg/kg i.p.) and KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA, adenosine, glutamate, and hydroxyl radical production. (biomedsearch.com)
  • The A3 receptor activation also led to an increase in extracellular levels of MMP9 in the supernatants of glioblastoma cells as evaluated by ELISA and gelatine zymography assays. (unife.it)
  • The adenosine receptors are the primary extracellular targets of caffeine. (iospress.com)
  • Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function (by pharmacological inhibition or in P2Y(2)(-/-) mice). (nih.gov)
  • Accordingly, the tissue hypoxia caused by limited blood supply may lead to an increase of local adenosine levels, probably because of insufficient ATP production and the inhibition of adenosine-metabolizing enzyme ( 14 , 15 , 16 ). (jimmunol.org)
  • 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)
  • Cellular adenosine transporte uptake of oTR but not adenosine receptors was involved in the growth inhibition. (alliedacademies.org)
  • In particular, the activation of the A3 receptor on this cellular type leads to the inhibition of degranulation and superoxide anion production with consequent anti-inflammatory effects. (unife.it)
  • Activation of receptors A 3 is also associated with multiple systems of second messengers, for example, inhibition of adenylate cyclase and stimulation of phospholipase C, and D. (russianpatents.com)
  • Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. (wikipathways.org)
  • these activated receptors act as transcription factors, regulating gene expression that results in the inhibition of cell proliferation, induction of cell differentiation, and apoptosis of both normal cells and tumor cells. (blogspot.com)
  • Adenosine receptors are a family of G protein-coupled receptors with increased attention as drug targets on different indications. (usc.es)
  • Effects of caffeine could be mediated by its action on several different targets such as cAMP phosphodiesterase, phosphatidylinositol-3 kinase, and adenosine receptors ( 1 , 2 ). (jimmunol.org)
  • Convergent is conducting advanced human trials relating to prostate cancer treatments involving peptide receptor radionuclide therapy that targets the prostate-specific membrane antigen on prostate cancer cells. (bioworld.com)
  • Jacobson and Gao (2006) Adenosine receptors as therapeutic targets. (scbt.com)
  • Adenosine receptors (AR) have been considered as potential therapeutic targets in neurodegenerative diseases, such as glaucoma. (arvojournals.org)
  • The development of genetic mutant mice deficient in adenosine receptors and other signaling molecules has allowed targeted inquiry into the molecular targets by which caffeine elicits its biological effects on behavior and gene expression. (iospress.com)
  • Over the last few years we have focused on many drug targets (adenosine A1, A2A and A3 receptors, the mGlu2 receptor and a classic 'anti-target', the hERG channel) to explore this notion. (universiteitleiden.nl)
  • 1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson's disease (PD), senile dementia and depression (1). (units.it)
  • 1] Several classes of heterocyclic derivatives have been reported as AR antagonists. (units.it)
  • On the basis of obtained results, the optimization of substitutions allow us, after 4 series (147compounds) of [1,2,4]triazolo[1,5-c]pyrimidine derivatives, to discover a potent and selective A3 AR antagonist, with a Ki of 0.47 nM. (units.it)
  • Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A 1 and A 2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. (wikipedia.org)
  • Benzofuran derivatives have shown biological activities, ranging from antifungal and antimicrobial properties to acting as antagonists for the H3 receptor and angiotensin II. (sigmaaldrich.com)
  • Epub 2007 Aug 1.New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. (nus.edu.sg)
  • Perreira et al (2005) "Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists. (scbt.com)
  • Cytokinin ribosides (N6-substituted adenosine derivatives) are nucleoside analogues that have shown anticancer activity both in vitro and in vivo in mammals [ 3 - 11 ]. (alliedacademies.org)
  • Truncated N 6 -substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4′-thioadenosines. (elsevier.com)
  • There is provided exceptionally stable and useful pro-drugs that are esters of N6-oxa, thia, thioxa and azacycloalkyl substituted adenosine derivatives that are selective adenosine type 1 receptor agonists, and as such, are potentially useful agents for the treatment cardiovascular diseases and central nervous system disorders. (justia.com)
  • An object of this invention are novel pro-drugs of heterocyclic substituted adenosine derivatives. (justia.com)
  • Another object of this invention are pro-drugs of heterocyclic substituted adenosine derivatives that are converted in the mammalian body to become useful A1 receptor agonists. (justia.com)
  • Still another object of this invention are pro-drugs of heterocyclic substituted adenosine derivatives that are useful for treating supraventricular tachycardias, including atrial fibrillation, atrial flutter, and AV nodal re-entrant tachycardia in mammals and especially humans. (justia.com)
  • Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. (iospress.com)
  • Therefore, we studied the influence of different agonists on antagonist affinity measurements for G i - and G s -coupled conformations of the adenosine A1-receptor in Chinese hamster ovary cells stably expressing the human adenosine A1-receptor and a cAMP-response element (CRE)-secreted placental alkaline phosphatase reporter gene. (aspetjournals.org)
  • The adenosine A 2B receptor , also known as ADORA2B , is a G-protein coupled adenosine receptor , and also denotes the human adenosine A 2b receptor gene which encodes it. (wikidoc.org)
  • 2008. A2B adenosine receptor gene deletion attenuates murine colitis. (springer.com)
  • Macrophages express membrane proteins that function as receptors for PtdSer (e.g. (elifesciences.org)
  • Adenosine A 1 and A 3 receptors are coupled to inhibitory G proteins, while A 2A and A 2B receptors are coupled to stimulatory G proteins [ 2 ]. (intechopen.com)
  • A2A and A2B ARs are Gs-coupled, while A1 and A3 ARs inhibit cAMP production via Gi proteins. (bvsalud.org)
  • The extent to which this finding applies to other G protein-coupled receptors and their interaction with different G proteins is unknown. (aspetjournals.org)
  • This was true even when the receptor was shown, in the same assay, to exist in two different conformational states coupled to two different G proteins. (aspetjournals.org)
  • Initially, we introduced on the bicyclic scaffold the same substituents those give affinity and selectivity at the A3 AR in the PTP nucleus. (units.it)
  • As the more widely dispersed receptor, adenosine A 2 is divided into two receptors on the basis of high- and low-affinity for adenosine, A 2A and A 2B [ 4 ]. (intechopen.com)
  • However, the antagonist affinity values measured at the G i -coupled and G s -coupled conformations of the receptor were the same in both functional responses and whole-cell binding. (aspetjournals.org)
  • Consequently, antagonist affinity measurements at a given species homolog of a particular receptor should remain constant regardless of the method used to measure it, provided that the chemical composition of the receptor has not changed. (aspetjournals.org)
  • Changes in antagonist affinity measurements have been noted at all human β-adrenoceptors. (aspetjournals.org)
  • Antagonist affinity estimates at many GPCRs may indeed depend upon the nature of the agonist used. (aspetjournals.org)
  • We tested a panel of naturally occurring nucleosides for their affinity towards adenosine receptors. (duhnnae.com)
  • 2-Chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA)--a high affinity agonist radioligand for A1 adenosine receptors. (wikipathways.org)
  • Since caffeine has similar affinity for several adenosine receptors, it has been difficult to determine which receptor subtypes mediate caffeine's effects using pharmacological tools. (iospress.com)
  • Another significant thermodynamic aspect, which characterizes the membrane receptors is the linearity of the van't Hoff plots in the temperature range usually investigated (0-35°C) indicating that the heat capacity value (DCp°) of the binding equilibrium is nearly zero, a phenomenon which is not usual in reactions involving biomacromolecules in solution (Sturtevant 1977). (stainlessqa.com)
  • This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. (wikidoc.org)
  • In addition to plasma membrane G protein-coupled chemokine receptors, small molecules can be designed to block intracellular enzymes that control signaling pathways. (biomedcentral.com)
  • We also noted that the A3 receptor stimulation led to increased levels of MMP9 protein in cellular extracts of U87MG cells, through phosphorylation of ERK1 / 2, JNK, Akt / PKB and the transcription factor AP-1. (unife.it)
  • Finally, as for the physiological relevance of the A3 receptor-mediated stimulation of MMP-9 we found that the A3 agonist was responsible for an increase of the invasive ability of U87MG cells. (unife.it)
  • Stimulation of the A1 adenosine receptor induces two distinct physiological responses. (justia.com)
  • Stimulation of the adenosine A1 receptor accordingly shortens the duration and decreases the amplitude of the action potential of AV nodal cells and subsequently prolongs the refractory period of the cells. (justia.com)
  • Stimulation of both A3 and A2A causes reduction in the scotopic ERG b-wave. (hi.is)
  • Now, a team of researchers from the University of South Carolina has hypothesized that the blockade of adenosine receptors by caffeine may be the most likely mechanism of CNS stimulation and delayed fatigue. (innovations-report.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)
  • The roles of the 1-, 2- and 3-ARs as well as NO were explored by using the selective antagonists CGP-20712A (300 nM), ICI -18551 (50 nM), SR59230A (100 nM) and NOS inhibitors L-NAME (50 μM) or LNNA (50 μM) respectively. (sun.ac.za)
  • 4) a selective alpha adrenergic agonist such as brimonidine and clonidine, 5) epinephrine, 6) Rho-kinase inhibitors, and 7) adenosine A3 receptor antagonists. (patentsencyclopedia.com)
  • 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)
  • Adenosine A1 receptor activation by adenosine and ATP produces cardiac arrest in the right atrium of Wistar rats predominantly through activation of potassium channels. (ovid.com)
  • We have used convergent modeling, mutagenesis and structure activity approaches to gather information about the three-dimensional structure of the receptors and its relationship to binding and activation functions. (nih.gov)
  • The results of this study, obtained by using real time RT-PCR and Western blotting, show that adenosine is able to increase both MMP9 mRNA and protein levels through the activation of the A3 adenosine receptor. (unife.it)
  • Overall, these results suggest that adenosine, through activation of the A3 receptor, modulates MMP9 protein levels and plays a role in the invasion of U87MG cells. (unife.it)
  • Blockade of the Adenosine A3 Receptor Attenuates Caspase 1 Activation in Renal Tubule Epithelial Cells and Decreases Interleukins IL-1β and IL-18 in Diabetic Rats. (unboundmedicine.com)
  • DPCPX (A1-AdoR antagonist) had no effect on the 1/ 2-PC-induced reduced infarct size or ERK p44/p42 and PKB activation. (sun.ac.za)
  • Both antagonists significantly reduced ERK and PKB activation in the trigger phase. (sun.ac.za)
  • MRS-1191 (A3-AdoR antagonist) blocked 1/ 2-PC when applied prior to index ischaemia or when added during early reperfusion, significantly inhibiting both ERK p44 and PKB activation. (sun.ac.za)
  • Adenosine receptor activation has been explored as a modulator of the inflammatory process that propagates osteoarthritis. (springer.com)
  • It has been reported that cartilage has enhanced regenerative potential when influenced by adenosine receptor activation. (springer.com)
  • 2016. Specific activation of A3, A2A and A1 adenosine receptors in CD73-knockout mice affects B16F10 melanoma growth, neovascularization, angiogenesis and macrophage infiltration. (springer.com)
  • Adenosine A2A antagonist is also believed to have neuroprotective effects. (intechopen.com)
  • A 2A receptors modulate processes accompanying brain injury in animal models of several neurological disorders and recently a neuroprotective potential of A 2A receptor antagonists has been suggested (Chen et al. (biomedsearch.com)
  • The progression of DN is associated with progressive and irreversible renal fibrosis and also high levels of adenosine. (unboundmedicine.com)
  • Targeting tyrosine kinases downstream of growth factor receptors might also reduce fibrosis in conditions like systemic sclerosis. (biomedcentral.com)
  • G protein-coupled receptor (GPCR) family members are integral to cell-cell communication and transduce signals to a wide range of chemical messengers. (aspetjournals.org)
  • Adenosine is a G-protein-coupled receptor and has four subtypes, which are A1, A2A, A2B, and A3. (intechopen.com)
  • Adenosine consists of four receptor subtypes: A 1 , A 2A , A 2B , and A 3 belonging to the superfamily of G-protein-coupled receptor. (intechopen.com)
  • Belongs to the G-protein coupled receptor 1 family. (abcam.com)
  • Sajjadi FG, Firestein GS: cDNA cloning and sequence analysis of the human A3 adenosine receptor. (drugbank.ca)
  • Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG: Molecular cloning and characterization of the human A3 adenosine receptor. (drugbank.ca)
  • A pyridine derivative that acts as a highly selective antagonist of A 3 receptor with excellent potency in both humans and rodents (K i = 18.9 nM for human A 3 R, and 113 nM for rat A 3 R). Exhibits only a trivial antagonistic activity towards A 1 and A 2A receptors (K i = 15.6 µM and 2.05 µM for rat A 1 R and A 2A R, respectively). (merckmillipore.com)
  • Several potent and selective A3 AR antagonists, e.g. 7, 8, 17 and 22 (Ki values of 5-9 nM at the human A3 AR) were prepared, which were much less potent at the rat orthologue. (bvsalud.org)
  • ZM241385, DPCPX, MRS1706 are inverse agonists with different relative intrinsic efficacies on constitutively active mutants of the human adenosine A2B receptor. (wikipathways.org)
  • Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. (wikipathways.org)
  • 2016. Adenosine as a multi-signalling guardian angel in human diseases: When, where and how does it exert its protective effects? (springer.com)
  • 2015. Down-regulation of the A3 adenosine receptor in human mast cells upregulates mediators of angiogenesis and remodeling. (springer.com)
  • SLV 320 is a potent and selective adenosine A1 receptor antagonist (Ki values are 1, 200, 398 and 3981 nM at human A1, A3, A2A and A2B receptors respectively). (emmx.com)
  • PSB 1115 is a highly selective, water-soluble, human A2B adenosine receptor antagonist. (emmx.com)
  • 10000 nM at human A2B, A1 and A3 receptors respectively. (emmx.com)
  • MRS 1706 is a potent and selective adenosine A2B receptor inverse agonist (Ki values are 1.39, 157, 112 and 230 nM for human A2B, A1, A2A and A3 receptors respectively). (emmx.com)
  • Nonselective adenosine A2A antagonists from natural compounds are caffeine and theophylline. (intechopen.com)
  • Effects of Adenosine Receptor Antagonists on the In Vivo LPS-Induced Inflammation Model of Parkinson's Disease. (biomedsearch.com)
  • Adenosine A 2A receptor antagonists emerged as a new promising non-dopaminergic therapy of Parkinson's disease (PD) (Schwarzschild et al. (biomedsearch.com)
  • Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. (wikipedia.org)
  • This review emphesizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. (eurekaselect.com)
  • The figurative elements of blood are important substrates on which adenosine plays multiple physiological functions. (unife.it)
  • We are interested in correlating structure of receptors and small molecular drugs with pharmacological properties. (nih.gov)
  • Substances developed as potent and selective agents acting through adenosine and P2 receptors have proven useful as pharmacological probes and have potential for treating diseases of the central nervous system, immune system, and cardiovascular system. (nih.gov)
  • From pharmacological experiments we had already learned that the two molecules, BMS-681 and CCR2-RA-[R], reinforced their binding to the receptor. (universiteitleiden.nl)
  • Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. (ovid.com)
  • The effects of adenosine, CPA and ATP were inhibited by DPCPX, a selective adenosine A1 receptor antagonist. (ovid.com)
  • In the heart of the receptors And 1 mediate negative inotropic, chronotropic and dromotropic effects of adenosine. (russianpatents.com)
  • Therefore the aim of this study was to evaluate the involvement of adenosine on the regulation of metalloproteinases and in particular of MMP9 in U87MG glioblastoma cells. (unife.it)
  • The most widely dispersed receptor is the A 3 receptor which can be found in the kidney, testis, lung, mast cells, eosinophils, neutrophils, heart, and the brain cortex [ 4 ]. (intechopen.com)
  • In these reviews we summarized the status of the art on the role of the A3 receptor in different types of immune cells including neutrophils, eosinophils, lymphocytes, monocytes, macrophages and dendritic cells. (unife.it)
  • Recent studies have shown the presence of A3 receptors on neutrophils, which represent the majority of circulating leukocytes and are the first cells to be recruited into a site of tissue inflammation in defending the body against infection. (unife.it)
  • BAY 60-6583 is a potent adenosine A2B receptor agonist that decreases fMLP-induced superoxide production in neutrophils at low concentrations (1-10 nM). (emmx.com)
  • This review summarizes the role adenosine receptor ligation plays in chondrocyte homeostasis and regeneration of articular cartilage damaged in osteoarthritis. (springer.com)
  • The purpose of this study was to examine what role adenosine receptors may play in the generation of the ERG. (hi.is)
  • The adenosine receptors are commonly known for their antagonists caffeine and theophylline , whose action on the receptors produces the stimulating effects of coffee , tea and chocolate . (wikipedia.org)
  • After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. (drugbank.ca)
  • Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. (drugbank.ca)
  • Theophylline is a non-specific adenosine antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects and some of its anti-asthmatic effects. (chemeurope.com)
  • Specific A 1 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3- dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine ( CCPA ). (wikipedia.org)
  • The role of adenosine and the adenosine A1, A3, A2A and A2B receptors was studied by using adenosine deaminase and the selective antagonists DPCPX (1 μM), MRS 1191(1 μM), ZM241385 (1 μM) and MRS1754 (1 μM). (sun.ac.za)
  • DPCPX is a potent and selective A1 adenosine receptor antagonist, both in vitro and in vivo. (emmx.com)
  • Adenozinski A 2A receptor ( ADORA2A ) je adenozinski receptor . (wikipedia.org)
  • Adenozinski A 2B receptor ( ADORA2B ) je G-protein spregnuti adenozinski receptor . (wikipedia.org)
  • Adenosine acts as a powerful signaling molecule via four distinct G protein-coupled receptors, designated A1, A2A, A2B and A3 adenosine receptors (ARs). (bvsalud.org)
  • Docking and molecule dynamic simulation studies using the crystal structure of the A1 AR and a homology model of the A3 AR were performed to rationalize the observed structure-activity relationships. (bvsalud.org)
  • Some surface receptors such as G-protein-coupled receptors represent another class of molecule that can be inhibited by small-molecule compounds. (biomedcentral.com)
  • A non-sedating ophthalmic antihistamine that antagonizes histamine H1 receptors (IC 50 = 1.58 nM) and prevents the release of pro-inflammatory mediators from mast cells and eosinophils. (thomassci.com)
  • This agent exhibits no anticholinergic activities and does not antagonize histamine H2 receptors. (termsreign.cf)
  • PSB 36 is a Potent and selective A1 adenosine receptor antagonist with binding affinities of 0.12, 187, 552, 6500 and 2300 nM for rA1, hA2B, rA2A, rA3 and hA3 receptors respectively. (emmx.com)
  • CV 1808, a adenosine A2 receptor agonist, is coronary vasodilator, antihypertensive and antipsychotic following systemic administration in vivo. (emmx.com)
  • Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). (wikipedia.org)
  • The genetic elimination of A2A adenosine receptors (A2AR) was shown to disengage the critical immunosuppressive mechanism and cause the dramatic exacerbation of acute inflammatory tissue damage by T cells and myeloid cells. (jimmunol.org)
  • the respective roles of the A1-, A2-, A3-adenosine receptors as well as the involvement of the PI3-K/PKB/Akt and ERKp44/p42 signal transduction pathways, in the cardioprotective phenomemon of -adrenergic preconditioning and (iv) the contribution of the mitochondrial KATP channels (mKATP), reactive oxygen species and NO to the mechanism of -AR-induced cardioprotection. (sun.ac.za)
  • 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)
  • In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. (wikipathways.org)
  • As adenosine's role in maintaining chondrocyte homeostasis at the cellular and molecular levels is explored, successful in vivo applications of adenosine delivery for cartilage repair continue to be reported. (springer.com)
  • It also reports on all the modalities reported for delivery of adenosine through in vivo applications. (springer.com)
  • In a mouse model of infarction the A3 selective agonist CP-532,903 protected against myocardial ischemia and reperfusion injury. (wikipedia.org)
  • Carolina rinse solution, adenosine, nisoldipine, pentoxifylline and prostaglandin E1 reduce graft failure from storage/reperfusion injury. (duke.edu)
  • [3] For instance, both A 1 receptors and A 2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A 2A receptor also has broader anti-inflammatory effects throughout the body. (wikipedia.org)
  • This study suggests an unappreciated "man-made" immunological pathogenesis whereby consumption of the food-, beverage-, and medication-derived adenosine receptor antagonists may modify an individual's inflammatory status and lead to excessive organ damage during acute inflammation. (jimmunol.org)
  • The A2A adenosine receptor (A2AR) has been shown to be a critical and nonredundant negative regulator of immune cells in protecting normal tissues from inflammatory damage. (pnas.org)
  • Adenosine A 1 receptor can be found in adipose tissue, heart muscle, and inflammatory cells. (intechopen.com)
  • Antagonists for A1 and A3 ARs may be useful for the treatment of (neuro)inflammatory diseases including acute kidney injury and kidney failure, pulmonary diseases, and Alzheimer's disease. (bvsalud.org)
  • Adenosine A3 receptors are G protein-linked receptors that functionality in body structure and intracellular signaling and are inquisitive about inflammatory responses and mediating cellphone proliferation and mobilephone demise. (stainlessqa.com)
  • The anti-inflammatory activity of methotrexate, which is mediated by increased adenosine release, is considered to be most important for its clinical effect on psoriasis [ 2 , 3 ]. (omicsonline.org)
  • Disclosed are (N)-methanocarba adenine nucleosides, e.g., of the formula (I): as A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein A, a, R2, and R3 are as defined in the specification. (nih.gov)