Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Alkynes: Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Receptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Receptor, Adenosine A3: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Receptor, Adenosine A2B: A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Exercise Test: Controlled physical activity which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used.Tomography, Emission-Computed, Single-Photon: A method of computed tomography that uses radionuclides which emit a single photon of a given energy. The camera is rotated 180 or 360 degrees around the patient to capture images at multiple positions along the arc. The computer is then used to reconstruct the transaxial, sagittal, and coronal images from the 3-dimensional distribution of radionuclides in the organ. The advantages of SPECT are that it can be used to observe biochemical and physiological processes as well as size and volume of the organ. The disadvantage is that, unlike positron-emission tomography where the positron-electron annihilation results in the emission of 2 photons at 180 degrees from each other, SPECT requires physical collimation to line up the photons, which results in the loss of many available photons and hence degrades the image.Myocardial Perfusion Imaging: The creation and display of functional images showing where the blood is flowing into the MYOCARDIUM by following over time the distribution of tracers injected into the blood stream.Thallium Radioisotopes: Unstable isotopes of thallium that decay or disintegrate emitting radiation. Tl atoms with atomic weights 198-202, 204, and 206-210 are thallium radioisotopes.Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)Radiopharmaceuticals: Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161)Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography: Tomography using single-photon emitting RADIONUCLIDES to create images that are captured in times corresponding to various points in the cardiac cycle.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Apiaceae: A large plant family in the order Apiales, also known as Umbelliferae. Most are aromatic herbs with alternate, feather-divided leaves that are sheathed at the base. The flowers often form a conspicuous flat-topped umbel. Each small individual flower is usually bisexual, with five sepals, five petals, and an enlarged disk at the base of the style. The fruits are ridged and are composed of two parts that split open at maturity.Acorus: A plant genus of the family ACORACEAE, order Arales, subclass Arecidae most notable for Acorus calamus L. root which contains asarone and has been used in TRADITIONAL MEDICINE.Pimenta: A plant genus in the family MYRTACEAE, order Myrtales, subclass Rosidae. It is best known for allspice from the dried berry of Pimenta diocia.Piper nigrum: A plant species in the PIPERACEAE plant family. It is a common spice on foods and is used medicinally to increase gastrointestinal assimilation of other supplements and drugs. Piperine is a key component. Black pepper is picked unripe and heaped for a few days to ferment. White Pepper is the ripe fruit dehulled by maceration in water.Myrtaceae: The myrtle plant family of the order Myrtales. It includes several aromatic medicinal plants such as EUCALYPTUS.Acoraceae: A plant family of the order Arales, subclass Arecidae, class Liliopsida (monocot).Black Pepper: A common spice from fruit of PIPER NIGRUM. Black pepper is picked unripe and heaped for a few days to ferment. White Pepper is the ripe fruit dehulled by maceration in water. Piperine is a key component used medicinally to increase gastrointestinal assimilation of other supplements and drugs.Spices: The dried seeds, bark, root, stems, buds, leaves, or fruit of aromatic plants used to season food.Cuscuta: A plant genus of the family Cuscutaceae. It is a threadlike climbing parasitic plant that is used in DRUGS, CHINESE HERBAL.Asteraceae: A large plant family of the order Asterales, subclass Asteridae, class Magnoliopsida. The family is also known as Compositae. Flower petals are joined near the base and stamens alternate with the corolla lobes. The common name of "daisy" refers to several genera of this family including Aster; CHRYSANTHEMUM; RUDBECKIA; TANACETUM.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Biomedical Research: Research that involves the application of the natural sciences, especially biology and physiology, to medicine.Social Sciences: Disciplines concerned with the interrelationships of individuals in a social environment including social organizations and institutions. Includes Sociology and Anthropology.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Medical Missions, Official: Travel by a group of physicians for the purpose of making a special study or undertaking a special project of short-term duration.Missions and Missionaries: To be used for articles pertaining to medical activities carried out by personnel in institutions which are administered by a religious organization.Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.Cycloleucine: An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Receptor, Metabotropic Glutamate 5: A type I G protein-coupled receptor mostly expressed post-synaptic pyramidal cells of the cortex and CENTRAL NERVOUS SYSTEM.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Scleral Diseases: General disorders of the sclera or white of the eye. They may include anatomic, embryologic, degenerative, or pigmentation defects.Myopia, Degenerative: Excessive axial myopia associated with complications (especially posterior staphyloma and CHOROIDAL NEOVASCULARIZATION) that can lead to BLINDNESS.Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock (see SHOCK).Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Cataract: Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)Retinal Dystrophies: A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Electrooculography: Recording of the average amplitude of the resting potential arising between the cornea and the retina in light and dark adaptation as the eyes turn a standard distance to the right and the left. The increase in potential with light adaptation is used to evaluate the condition of the retinal pigment epithelium.Acute Lung Injury: A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Lung Injury: Damage to any compartment of the lung caused by physical, chemical, or biological agents which characteristically elicit inflammatory reaction. These inflammatory reactions can either be acute and dominated by NEUTROPHILS, or chronic and dominated by LYMPHOCYTES and MACROPHAGES.Respiratory Distress Syndrome, Adult: A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Skin Window Technique: A technique to study CELL MIGRATION in the INFLAMMATION process or during immune reactions. After an area on the skin is abraded, the movement of cells in the area is followed via microscopic observation of the exudate through a coverslip or tissue culture chamber placed over the area.
(1/229) Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats.

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

(2/229) Comparative pharmacological studies on the A2 adenosine receptor agonist 5'-n-ethyl-carboxamidoadenosine and its F19 isotope labelled derivative.

Adenosine receptors are expressed in various mammalian tissues where they mediate the effects of adenosine on cellular functions through a number of signalling mechanisms. 18F-NECA is the positron-emitting derivative of the A(2)-receptor agonist NECA (5'-n-ethyl-carboxamidoadenosine) and is a radioligand for PET imaging of adenosine receptors. Contractility and relaxation studies were performed on guinea pig atrial myocardium, pulmonary artery, and thoracic aorta to compare the pharmacological effects of NECA and F-NECA (a non-emitting derivative) on tissues. Furthermore, the effect of NECA and F-NECA on the potassium conductance was investigated in DDT1 MF-2 smooth muscle cells with the patch-clamp technique. Both NECA and F-NECA reduced the contractile force in atrial myocardium and evoked phasic contraction in pulmonary artery (A(1) adenosine-receptor-mediated actions) in a dose dependent manner; however, the apparent affinity was lower for F-NECA. No difference was found in relaxation induced by these compounds in 1 microM noradrenaline-precontracted aorta and pulmonary artery (in the presence of DPCPX, an A(1) adenosine receptor antagonist, tissue containing A(2B) adenosine receptors). NECA (5 microM) and F-NECA (5 microM) also decreased the peak current and accelerated activation and inactivation properties of the potassium channels, but F-NECA was less effective. These results suggest that while NECA and F-NECA are equivalent agonists of vascular A(2B) receptors, they mediate different changes of some parameters. When evaluating the data obtained by the use of radiolabelled ligands, one has to take into consideration the possible physiological effects of the ligands besides its binding properties to tissues.  (+info)

(3/229) Protection from ischemic liver injury by activation of A2A adenosine receptors during reperfusion: inhibition of chemokine induction.

Ischemia-reperfusion (I/R) injury occurs as a result of restoring blood flow to previously hypoperfused vessels or after tissue transplantation and is characterized by inflammation and microvascular occlusion. We report here that 4-[3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2 -yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester (ATL146e), a selective agonist of the A(2A) adenosine receptor (A(2A)AR), profoundly protects mouse liver from I/R injury when administered at the time of reperfusion, and protection is blocked by the antagonist ZM241385. ATL146e lowers liver damage by 90% as assessed by serum glutamyl pyruvic transaminase and reduces hepatic edema and MPO. Most protection remains if ATL146e treatment is delayed for 1 h but disappears when delayed for 4 h after the start of reperfusion. In mice lacking the A(2A)AR gene, protection by ATL1465e is lost and ischemic injury of short duration is exacerbated compared with wild-type mice, suggesting a protective role for endogenous adenosine. I/R injury causes induction of hepatic transcripts for IL-1alpha, IL-1beta, IL-1Ra, IL-6, IL-10, IL-18, INF-beta, INF-gamma, regulated on activation, normal T cell expressed, and presumably secreted (RANTES), major intrinsic protein (MIP)-1alpha, MIP-2, IFN-gamma-inducible protein (IP)-10, and monocyte chemotactic protein (MCP)-1 that are suppressed by administering ATL146e to wild-type but not to A(2A)AR knockout mice. RANTES, MCP-1, and IP-10 are notable as induced chemokines that are chemotactic to T lymphocytes. The induction of cytokines may contribute to transient lymphopenia and neutrophilia that occur after liver I/R injury. We conclude that most damage after hepatic ischemia occurs during reperfusion and can be blocked by A(2A)AR activation. We speculate that inhibition of chemokine and cytokine production limits inflammation and contributes to tissue protection by the A(2A)AR agonist ATL146e.  (+info)

(4/229) Input-specific modulation of neurotransmitter release in the lateral horn of the spinal cord via adenosine receptors.

Activation of adenosine A2A receptors (A2ARs) in the CNS produces a variety of neuromodulatory actions dependent on the region and preparation examined. In autonomic regions of the spinal cord, A1R activation decreases excitatory synaptic transmission, but the effects of A2AR stimulation are unknown. We sought to determine the location and function of the A2ARs in the thoracic spinal cord, focusing on the intermediolateral cell column (IML). A2AR immunoreactivity was observed throughout the gray matter, with particularly dense immunostaining in regions containing sympathetic preganglionic neurons (SPNs), namely, the IML and intercalated nucleus. Electron microscopy revealed A2AR immunoreactivity within presynaptic terminals and in postsynaptic structures in the IML. To study the functional relevance of these A2ARs, visualized whole-cell patch-clamp recordings were made from electrophysiologically identified SPNs and interneurons within the IML. The A2AR agonist c2-[p-(carboxyethyl)phenethylamino]-5'-N-ethylcarboxyamidoadenosine (CGS 21680) had no significant effect on EPSPs but increased the amplitude of IPSPs elicited by stimulation of the lateral funiculus. These effects were attributable to activation of presynaptic A2ARs because CGS 21680 application altered the paired pulse ratio. Furthermore, neurons in the IML that have IPSPs increased via A2AR activation also receive excitatory inputs that are inhibited by A1R activation. These data show that activating A2ARs increase inhibitory but not excitatory transmission onto neurons in the IML. Simultaneous activation of A1Rs and A2ARs therefore could facilitate inhibition of the postsynaptic neuron, leading to an overall reduction of sympathetic nervous activity.  (+info)

(5/229) Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors.

Activation of rat adenosine2A receptors (A2A R) dilates preglomerular microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs). Incubation of PGMV with a selective A2A R agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 100 microM), increased isolated PGMV EET levels to 7.57+/-1.53 ng mg-1 protein from 1.06+/-0.22 ng mg-1 protein in controls (P<0.05), without affecting hydroxyeicosatetraenoic acid (HETE) levels (10.8+/-0.69 vs 11.02+/-0.74 ng mg-1 protein). CGS 21680-stimulated EETs was abolished by preincubation with an A2A R antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phe nol (ZM241385) (100 microM). A selective epoxygenase inhibitor, methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; 12 microM) prevented CGS 21680-induced increase in EETs, indicating inhibition of de novo synthesis of EETs. In pressurized (80 mmHg) renal arcuate arteries (110-130 microm) preconstricted with phenylephrine (20 nM), superfusion with CGS 21680 (0.01-10 microM) increased the internal diameter (i.d.) concentration-dependently; vasodilation was independent of nitric oxide and cyclooxygenase activity. CGS 21680 (10 microM) increased i.d. by 32+/-6 microm; vasodilation was prevented by inhibition of EET synthesis with MS-PPOH. Addition of 3 nM 5,6-EET, 8,9-EET and 11,12-EET increased i.d. by 53+/-9, 17+/-4 and 53+/-5 microm, respectively, whereas 14,15-EET was inactive. The responses to 5,6-EET were, however, significantly inhibited by indomethacin. We conclude that 11,12-EET is the likely mediator of A2A R-induced dilation of rat PGMV. Activation of A2A R coupled to de novo EET stimulation may represent an important mechanism in regulating preglomerular microvascular tone. British Journal of Pharmacology (2004) 141, 441-448. doi:10.1038/sj.bjp.0705640  (+info)

(6/229) Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging.

BACKGROUND: Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. METHODS AND RESULTS: In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related. CONCLUSIONS: The selective adenosine A2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.  (+info)

(7/229) Role of adenosine A2A receptor in the regulation of gastric somatostatin release.

Adenosine has been demonstrated to inhibit gastric acid secretion. In the rat stomach, this inhibitory effect may be mediated indirectly by increasing the release of somatostatin-like immunoreactivity (SLI). Results show that adenosine analogs augmented SLI release in the isolated vascularly perfused rat stomach. The rank order of potency of the analogs in stimulating SLI release was 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) approximately 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine > R-(-)-N(6)-(2-phenylisopropyl)adenosine >1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-beta-d-ribofu ranuronamide > N(6)-cyclopentyladenosine approximately N(6)-cyclohexyladenosine > S-(+)-N(6)-(2-phenylisopropyl) adenosine, suggesting the involvement of the A(2A) receptor. In agreement, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a] [1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385), an A(2A) receptor antagonist, was shown to abolish the adenosine- and CGS 21680-stimulated SLI release. Immunohistochemical studies reveal the presence of A(2A) receptor immunoreactivity on the gastric plexi and mucosal D-cells, but not on parietal cells and G-cells, suggesting that adenosine may act directly on D-cells or indirectly on the gastric plexi to augment SLI release. The present study also demonstrates that the structure of the mucosal A(2A) receptor is identical to that in the rat brain, and that alternative splicing of this gene does not occur. A real-time reverse transcription-polymerase chain reaction assay has also been established to quantify the levels of A(2A) receptor mRNA. Results show that gastric tissues contained significantly lower levels of A(2A) receptor mRNA compared with the striatum. The lowest level was detected in the mucosa. In conclusion, adenosine may act on A(2A) receptors to augment SLI release and consequently control gastric acid secretion.  (+info)

(8/229) A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells.

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.  (+info)

*  Adenosine A2A receptor
... adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels". ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ...
*  Adenosine A3 receptor
... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... 1997). "Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ...
*  GPCR oligomer
"Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes ... "A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers". Proc. Natl. Acad. Sci. U.S.A. ... In 1991, the phenomenon of receptor crosstalk was observed between adenosine A2A (A2A) and dopamine D2 receptor (DRD2) thus ... two adenosine A2A receptors and two dopamine D2 receptors). Maggio and co-workers showed in 1993 the ability of the muscarinic ...
*  Adenosine
The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ... and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor. ... In the US, Adenosine is marketed as Adenocard. In India Adenosine is sold as Adenoscan (Cipla) All adenosine receptor subtypes ... Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor. However, while it is able to increase ...
*  Adenosine A1 receptor
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... A1 receptors are also present in smooth muscle throughout the vascular system. The adenosine A1 receptor has been found to be ...
*  Thromboregulation
These signaling elements include thromboxane A2, receptor type α, phospholipase Cβ3, and IP3 receptors. Signalization in ... It has been shown that collagen, exposed after the injury to the endothelial cover of the vessel, plays as an agonist in ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). ... TX2 effects are mediated by G protein-coupled receptors, subtypes TPα and TPβ. Both receptors mediate phospholipase C ...
*  5-HT1D receptor
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... This is a valuable guide to design potential 5HT1D receptor agonists. When sumatriptan binds there is major conformational ... 5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding ... Goadsby, P.J., Serotonin 5-HT1B/1D receptor agonists in migraine - Comparative pharmacology and its therapeutic implications. ...
*  Nociceptin receptor
... full agonist at NOP, μ-opioid and δ-opioid receptors, partial agonist at κ-opioid receptor) Etorphine MCOPPB (full agonist) MT- ... Fukuda K, Shoda T, Morikawa H, Kato S, Mima H, Mori K (1998). "Activation of phospholipase A2 by the nociceptin receptor ... causing an intracellular decrease in cyclic adenosine monophosphate(cAMP) levels, an important second messenger for many signal ... receptor agonists in acute versus chronic pain: studies with bifunctional NOP/μ receptor agonists in the sciatic nerve ligation ...
*  Multiple electrode aggregometry
Adenosine diphosphate (ADP) is a platelet agonist. When it is added to saline-diluted whole blood in the test cuvette, it ... Thrombin receptor activating peptide-6 (TRAP-6) activates platelets through the thrombin receptor protease activated receptor-1 ... and PGH2 is then converted to thromboxane A2 (TXA2) by thromboxane synthase. TXA2 increases platelet aggregation, promotes ... Activation of the P2Y1 receptor initiates platelet aggregation in response to ADP. The P2Y1 receptor is required for ADP- ...
*  Theophylline
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...
*  Biochemical cascade
PAR1 and PAR4 receptors), platelet-derived thromboxane A2 (TxA2) (TP receptor) and ADP (P2Y1 and P2Y12 receptors) that is ... Adenosine acts by binding to purinergic receptors and influencing adenilyl cyclase activity and the formation of cAMP and PKA ... In general terms, platelet activation initiated by agonist takes to a signaling cascade that leads to an increase of the ... Therefore, there are four main transmembrane receptor types: G protein coupled receptors (GPCRs), tyrosine kinase receptors ( ...
*  Prostaglandin DP1 receptor
... the DP1-dependent stimulation of adenosine formation and subsequent simulation of the Adenosine A2A receptor by adenosine. In ... "Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist ... thromboxane A2, with PGD2 being more than 100-fold more potent than PGE2 in binding to and stimulating DP1. (http://www. ... Prostaglandin receptors Prostanoid receptors Prostaglandin DP2 receptor Eicosanoid receptor GRCh38: Ensembl release 89: ...
*  Molecular and epigenetic mechanisms of alcoholism
... receptors are glutamate receptors particularly important in long-term potentiation in neurons. These receptors have been linked ... Funk, C.K. and Koob, G.F. (2007). A CRF2 agonist administered into the central nucleus of the amygdala decreases ethanol self- ... Katsura, M., Shibasaki, M., Hayashida, S., Torigoe, F., Tsujimura, A., Ohkuma, S. (2006) Increase in expression of a1 and a2/d1 ... Pandey, S.C., Roy, A., Zhang, H. (2003). The decreased phosphorylation of cyclic adenosine monophosphate (cAMP) response ...
*  Arachidonate 5-lipoxygenase
The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular ... Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... As a second drug added to corticosteroids, leukotriene inhibitors appear inferior to Beta2-adrenergic agonist drugs in the ... may serve as a mobile lid over ALOX5's substrate-binding site An Adenosine triphosphate (ATP) binding site; ATP is crucial for ...
*  12-Hydroxyheptadecatrienoic acid
... trienoic acid as a thromboxane A2 receptor antagonist with minimal intrinsic activity". British Journal of Haematology. 101 (1 ... Syntheic BLT2 agonists may be useful for speeding the healing of chronic ulcerative wounds, particularly in patients with, for ... to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine ... BLT1 receptor) and its low affinity BLT2 receptor (Kd=23 nM); both receptors are G protein coupled receptors that, when ligand- ...
Yang Z, Sun W, Hu K (Apr 2012). "Molecular mechanism underlying adenosine receptor-mediated mitochondrial targeting of protein ... A myriad of agonists have also been shown to induce the translocation of PKCε from the cytosolic to particulate fraction in ... Perjés Á, Skoumal R, Tenhunen O, Kónyi A, Simon M, Horváth IG, Kerkelä R, Ruskoaho H, Szokodi I (2014). "Apelin increases ... Yang Z, Sun W, Hu K (Apr 2012). "Molecular mechanism underlying adenosine receptor-mediated mitochondrial targeting of protein ...
*  Neurotransmitter
Such drugs are called receptor agonists. An example of a receptor agonist is Valium, a benzodiazepine that mimics effects of ... Rinaman L (February 2011). "Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and ... Peptides: somatostatin, substance P, cocaine and amphetamine regulated transcript, opioid peptides Purines: adenosine ... Direct-binding agonists can be further characterized as full agonists, partial agonists, inverse agonists.[citation needed] ...
*  MicroRNA
Most commonly, enzymes known as adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine (A to I) transitions. ... miR-382 is the target for the dopamine receptor D1 (DRD1), and its overexpression results in the upregulation of DRD1 and delta ... December 2003). "High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ... Choi WY, Giraldez AJ, Schier AF (October 2007). "Target protectors reveal dampening and balancing of Nodal agonist and ...
A Category Names List - Drug Information Portal - U.S. National Library of Medicine  A Category Names List - Drug Information Portal - U.S. National Library of Medicine
Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ... Adenosine A2 Receptor Antagonists (8) • Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS. ...
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A Category Names List - Drug Information Portal - U.S. National Library of Medicine  A Category Names List - Drug Information Portal - U.S. National Library of Medicine
Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ... Adenosine A2 Receptor Antagonists (8) • Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS. ...
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2-Alkynyl derivatives of Adenosine-5-N-ethyluronamide (NECA): selective A2 adenosine receptor agonists with potent inhibitory...  2-Alkynyl derivatives of Adenosine-5'-N-ethyluronamide (NECA): selective A2 adenosine receptor agonists with potent inhibitory...
2-Alkynyl derivatives of Adenosine-5'-N-ethyluronamide (NECA): selective A2 adenosine receptor agonists with potent inhibitory ... 2-Alkynyl derivatives of Adenosine-5'-N-ethyluronamide (NECA): selective A2 adenosine receptor agonists with potent inhibitory ... The presence of an a-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to ... The presence of an a-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to ...
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Intravenous Regadenoson Versus Intravenous Adenoscan® for Fractional Flow Reserve (FFR) - Full Text View -  Intravenous Regadenoson Versus Intravenous Adenoscan® for Fractional Flow Reserve (FFR) - Full Text View -
Adenosine. Adenosine A2 Receptor Agonists. Coronary Artery Disease. Myocardial Ischemia. Coronary Disease. Heart Diseases. ... Purinergic P1 Receptor Agonists. Purinergic Agonists. Purinergic Agents. Neurotransmitter Agents. Molecular Mechanisms of ...
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Adenozinski A2A receptor - Wikipedia  Adenozinski A2A receptor - Wikipedia
1992). "Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature.". Eur. J. ... 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): ... a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels". Eur. J. Pharmacol. 213 ...
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Metabolic features of chronic fatigue syndrome | PNAS  Metabolic features of chronic fatigue syndrome | PNAS
2007) Adenosine A1 and A2 receptor agonists reduce endotoxin-induced cellular energy depletion and oedema formation in the lung ... Plasma adenosine was decreased in females (Table 3, Females). Plasma adenosine is produced from ATP and ADP released from cell ... 2011) P2 receptors and extracellular ATP: A novel homeostatic pathway in inflammation. Front Biosci (Schol Ed) 3:1443-1456. ... 2015) Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med 21(11):702 ...
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Small molecules activating TrkB receptor for treating a variety of CNS disorders<...  Small molecules activating TrkB receptor for treating a variety of CNS disorders<...
Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB ... Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB ... Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB ... Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB ...
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Search Articles | University of Toronto Libraries  Search Articles | University of Toronto Libraries
Adenosine A2 Receptor Antagonists - metabolism , Adenosine A2 Receptor Agonists - pharmacology , Adenosine A3 Receptor Agonists ... Receptor, Adenosine A2A - drug effects , Adenosine A2 Receptor Antagonists - pharmacology , Adenosine A2 Receptor Agonists - ... Receptor, Adenosine A2A - genetics , Molecular Docking Simulation , Adenosine A2 Receptor Agonists - chemistry , Adenosine A2 ... Adenosine A2A - metabolism , Adenosine A2 Receptor Antagonists - pharmacology , Animals , Adenosine A2 Receptor Agonists - ...
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Activation of nucleotide receptors with extracellular ATP and nucleotide analogues increased ... Regulation of plasma membrane ion transport by endogenous purinergic receptors was assessed in a distal renal (A6) cell line. ... In contrast to the adenosine A2 receptor agonist 5'-N-ethylcarboxamidoadenosine, nucleotide analogues had no discernible effect ... Neither the change in [Ca2+]i nor the stimulation of cotransport was abolished by the adenosine receptor antagonist 8-{4-[N-(2- ...
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Renal Adenosine in Health and Disease | Springer for Research & Development  Renal Adenosine in Health and Disease | Springer for Research & Development
... renal function in healthy and diseased kidney is mediated by activation of the four types of P1 purinergic adenosine receptors ... Agmon Y, Dinour D, Brezis M (1993) Disparate effects of adenosine A1- and A2-receptor agonists on intrarenal blood flow. Am J ... Levens N, Beil M, Schulz R (1991) Intrarenal actions of the new adenosine agonist CGS 21680A, selective for the A2 receptor. J ... Kim M, Chen SW, Park SW et al (2009) Kidney-specific reconstitution of the A1 adenosine receptor in A1 adenosine receptor ...
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CGS 21680 | Abcam  CGS 21680 | Abcam
... selective A2A agonist. Join researchers using high quality CGS 21680 from Abcam and achieve your mission, faster. ... CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity.. J Pharmacol Exp Ther 251:47-55 ... Adenosine receptors and their ligands.. Naunyn Schmiedebergs Arch Pharmacol 362:382-91 (2000). Read more (PubMed: 11111832) » ... Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By research area. Cancer. Cardiovascular. ...
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      - NECA
     Summary Report | CureHunter  Adenosine-5'-(N-ethylcarboxamide) - NECA Summary Report | CureHunter
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity. ... Subscribe to New Research on Adenosine-5'-(N-ethylcarboxamide) A stable adenosine A1 and A2 receptor agonist. Experimentally, ... 05/01/1998 - "The effect of serotonergic agents was studied on the adenosine A2 receptor agonist NECA-induced catalepsy in mice ... 01/01/1993 - "The adenosine agonists 5-N'-ethylcarboxamide-adenosine (NECA), N6-phenylisopropyladenosine (PIA) and N6- ...
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Alcohol in Moderation, Cardioprotection and Neuroprotection: Epidemiological Considerations and Mechanistic Studies  Alcohol in Moderation, Cardioprotection and Neuroprotection: Epidemiological Considerations and Mechanistic Studies
... administration of adenosine A2 receptor agonists, cell-permeant cyclic AMP analogs, or adenylyl cyclase activators (e.g., ... Adenosine A1 receptor blockade abolished the protection, suggesting a role of adenosine A1 receptor in cardioprotection. In ... Sensors include glutamate receptors (notably the NMDA receptor channel), adenosine receptors, and perhaps others coupled to Gi ... Pharmacologic inhibitor studies support this concept and indicated that adenosine A2 receptor occupancy is required for this ...
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NAVER Academic > Search...  NAVER Academic > Search...
Adenosine, analogs & derivatives, pharmacology, Adenosine A2 Receptor Agonists, Animals, Cell Line, Hypoxia-Inducible Factor 1 ... a role for MyD88 in the regulation of wound healing by adenosine A2A receptors.. 2007 Lisa Macedo et al. AMERICAN JOURNAL OF ... Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death of cerebrovascular cells.. 2007 Micha M M ... The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including ...
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US Patent for Dendrimers as molecular translocators Patent (Patent #  7,862,807 issued January 4, 2011) - Justia Patents Search  US Patent for Dendrimers as molecular translocators Patent (Patent # 7,862,807 issued January 4, 2011) - Justia Patents Search
... adenosine A2 receptor agonist (e.g., YT-146), CD5 antagonist (e.g., zolimomab), 5-lipoxygenase inhibitor (e.g., zileuton, ... adenosine agonists (e.g., GP-1-4683, ARA-100, and arasine analogs), adenosine A1 receptor agonists (e.g., Azaisotere, 2-chloro- ... alpha 2 agonists (e.g., SNAP-5083, SNAP-5608, and SNAP-5682), AMPA receptor agonists (e.g., heterocyclic compound SYM-1207, and ... EAA receptors, endothelin antagonists (e.g., SB 209670), endothelin receptor antagonists, excitatory amino acid agonists (e.g ...
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Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of...  Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of...
... 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 ... Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist ... Adenosine and ATP exert a negative chronotropic effect in the heart. This study aims to evaluate adenosine and P2 receptors and ...
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Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist | PNAS  Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist | PNAS
1991) Activity of N6-substituted 2-chloroadenosines at A1 and A2 adenosine receptors. J Med Chem 34(12):3388-3390. ... 2007) New fluorescent adenosine A1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains ... 2010) A novel highly selective adenosine A1 receptor agonist VCP28 reduces ischemia injury in a cardiac cell line and ischemia- ... Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. Celine ...
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Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.  - PubMed - NCBI  Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. - PubMed - NCBI
... a combined A1 and A2 adenosine receptor agonist that increases BBB permeability by increasing spaces between endothelial cells. ...
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  • A series of new 2-alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N-ethyluronamid(NECA) and of N-ethyl-l'-deoxy-l'-(6-amino-2-hexynyl-9H-purin-9-yl)-b-D-ribofuranuronamid(1e, HENECA), bearing hydroxy, amino, chloro, and cyano groups in the side chain, were synthesized. (
  • The presence of an a-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to compounds endowed with sub-nanomolar affinity in binding studies. (
  • EGF also potentiates the forskolin-induced stimulation of C-AMP but has no effect on the elevation of C-AMP caused by NECA (5′-[N-ethyl]-carboxamido adenosine), an adenosine A2-receptor agonist. (
  • To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (
  • Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (
  • Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (
  • ASP5854 ameliorated A(2A) agonist 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680)- and haloperidol-induced catalepsy in mice, with the minimum effective doses of 0.32 and 0.1 mg/kg, respectively, and it also improved haloperidol-induced catalepsy in rats at doses higher than 0.1 mg/kg. (
  • We found evidence that CGS21680 can increase the maximal BRET(2) signal between β-arrestin2(RLuc) and D(2L)R(GFP2) upon D(2)R activation, by increasing the potency of the D(2)R agonist to exert this action. (
  • The A2a specific agonist CGS21680 stimulated cAMP production but did not alter intracellular calcium concentrations in transfected 293 cells. (
  • Maggio and co-workers showed in 1993 the ability of the muscarinic M3 receptor and α2C-adrenoceptor to heterodimerize. (
  • Moreover, adenosine protects against renal ischemic reperfusion injury by the anti-inflammatory effect of enhancing the activity of regulatory T cell and by attenuating the inflammatory injury produced by neutrophils via A 2 AR activation. (
  • Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. (
  • This study aims to evaluate adenosine and P2 receptors and cellular signalling in cardiac arrest produced by purines in the heart. (
  • Sustained exposure of the cells to agonists at the IP prostanoid receptor results in a substantial decrease in cellular levels of the alpha-subunit of Gs (Gs alpha) [McKenzie and Milligan (1990) J. Biol. (
  • By contrast, equivalent treatments of the cells with agonists at either the A2 adenosine receptor or the secretin receptor have no measurable effect on cellular amounts of Gs alpha. (
  • In beta N22 cells the IP prostanoid receptor was expressed at similar levels to those in wild-type NG108-15 cells, and treatment with iloprost resulted in a similar down-regulation of cellular Gs alpha levels. (
  • These findings suggest that during pathological conditions such as inflammation or trauma, the significant amounts of cellular adenosine which are released may increase the production of NO by macrophage. (
  • The presence of an a-quaternary carbon such as the 3-hydroxy-3,5-dimethyl-1-hexynyl (12) and the 3-hydroxy-3-phenyl-1-butynyl(1 5) derivatives markedly reduced the antiaggregatory potency without affecting the A2 affinity. (
  • Adenosine receptors and their ligands. (
  • Guanylyl cyclase C (GC-C), the receptor for diarrheagenic enterotoxins and the paracrine ligands guanylin and uroguanylin, regulates intestinal secretion. (
  • We validate that the interaction of VCP746 with the A 1 AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A 1 AR ligands. (
  • Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects. (
  • The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. (
  • The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). (
  • Taken together, the results indicate that the antagonistic A(2A)R-D(2)R allosteric receptor-receptor interaction in A(2A)R-D(2)R heteromers favors β-arrestin2 recruitment to the D(2L)R protomer with subsequent cointernalization associated with a reduced time onset of Akt phosphorylation followed by a rapid dephosphorylation. (
  • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. (
  • To address possible mechanisms for stimulation of Na-K-Cl cotransport by the nucleotide receptor, I-125 efflux and patch-clamp studies were used to measure chloride secretion. (
  • Dibutyryl C-AMP has a negative effect on RPE cell proliferation while isoproterenol is ineffective.The data presented here suggest that after stimulation of EGF receptors, tyrosine-kinase-activated products can influence secondary messenger products produced from activation of β2-type (linked with C-AMP formation) and muscarinic (linked with InsPs production) receptors in RPE cells. (
  • Wound healing is impaired in MyD88-deficient mice: a role for MyD88 in the regulation of wound healing by adenosine A2A receptors. (
  • These results demonstrate that the phenomenon of agonist-induced specific G-protein down-regulation is determined by the levels of expression of the receptor. (
  • However, these analogues also possess good A1 receptor affinity resulting in low A2 selectivity. (
  • The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. (
  • G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins and tractable drug targets ( 1 , 2 ). (
  • The first direct evidence that GPCRs functioned as oligomers in vivo came from Overton and Blumer in 2000 by fluorescence resonance energy transfer (FRET) analysis of the α-factor receptor in the yeast Saccharomyces cerevisiae. (
  • In 2005, further evidence was provided that receptor oligomizeration plays a functional role in a living organism with regulatory implication. (
  • Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death of cerebrovascular cells. (
  • 300 fmol/mg of membrane protein of the receptor. (
  • The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. (
  • The gene encodes a protein which is one of several receptor subtypes for adenosine. (
  • In this role, A2AR functions similarly to programmed cell death-1 (PD-1) and cytotoxic t-lymphocyte associated protein-4 (CTLA-4) receptors, namely to suppress immunologic response and prevent associated tissue damage. (
  • A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. (
  • Autonomic nerves release ATP, which is processed into adenosine in the synaptic cleft. (
  • It has been shown that an A2AR agonist protects against ischemia-reperfusion injury in porcine allogeneic lung transplantation ( 23 ). (
  • The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. (
  • On the existence of a possible A2A-D2-β-Arrestin2 complex: A2A agonist modulation of D2 agonist-induced β-arrestin2 recruitment. (
  • Mass determination of β-adrenoceptors (1982) and muscarinic receptors (1983), supported the existence of homodimer or tetrameric complexes. (
  • In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. (
  • A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. (
  • Nucleotide receptors may effect their responses through primary activation of membrane chloride channels. (
  • Cumulative concentration-effect curves of adenosine and CPA resulted in a negative chronotropic effect culminating in cardiac arrest at 1000 μM (adenosine) and 1 μM (CPA). (
  • The adenosine A 1 receptor (A 1 AR) is an important target for cardioprotection, but current A 1 AR drugs are limited for this indication because of the occurrence of bradycardia as a major adverse effect mediated by the same receptor. (
  • Exposure of beta N22 cells to the beta-adrenergic agonist isoprenaline resulted maximally in some 55% decrease in membrane-associated levels of Gs alpha, without effect on membrane levels of Gi2 alpha, Gi3 alpha, G(o) alpha or Gq alpha/G11 alpha. (
  • Adenosine and its agonists had no effect on NOS activity when incubated alone with RAW 264.7 cells. (
  • Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function. (
  • Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of Wistar rats? (
  • 4-Aminopyridine, a blocker of potassium channels at 10 mM, prevented the cardiac arrest produced by adenosine and ATP, while BayK 8644, activator of calcium channels, did not prevent cardiac arrest. (
  • The hydrophobicity index (k') of the new nucleosides barely correlated with the binding data, whereas high k' values were associated with increased A2 vs A1 selectivity but with reduced activity in all unctional assays. (
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (
  • Nitrite production and NOS activity in the RAW 264.7 cells were increased up to 2.5 fold after co-exposure of the cells to LPS and adenosine or its agonists, as compared to LPS alone. (
  • Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (
  • Here, we show that the expression of a potential glucagon inhibitor, the adenosine A1 receptor (Adora1), is gradually diminished in α-cells of NOD mice, autoantibody-positive (AA + ) and overtly type 1 diabetic (T1D) patients during the progression of disease. (
  • The existence of receptor oligomers is a general phenomenon, whose discovery has superseded the prevailing paradigmatic concept of the function of receptors as plain monomers, and has far-reaching implications for the understanding of neurobiological diseases as well as for the development of drugs. (