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Titolo:
Inhibitory effects of SR141716A on G-protein activation in rat brain
Autore:
Sim-Selley, LJ; Brunk, LK; Selley, DE;
Indirizzi:
Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Virginia Commonwealth Univ, Med Coll Virginia, Inst Drug & Alcohol Studies, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 2-3, volume: 414, anno: 2001,
pagine: 135 - 143
SICI:
0014-2999(20010302)414:2-3<135:IEOSOG>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
CANNABINOID RECEPTOR ANTAGONIST; NUCLEOTIDE-BINDING PROTEINS; IN-VIVO CHARACTERIZATION; GAMMA-S AUTORADIOGRAPHY; INVERSE AGONIST; ACETYLCHOLINE-RELEASE; SELECTIVE ANTAGONIST; CARDIAC MEMBRANES; CB2 RECEPTORS; 141716A;
Keywords:
cannabinoid receptor; [S-35]GTP gamma S binding; G-protein-coupled receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Sim-Selley, LJ Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, 1112 E Clay St,Box 980524, Richmond, VA 23298 USA Virginia Commonwealth Univ 1112 E Clay St,Box 980524 Richmond VA USA 23298
Citazione:
L.J. Sim-Selley et al., "Inhibitory effects of SR141716A on G-protein activation in rat brain", EUR J PHARM, 414(2-3), 2001, pp. 135-143

Abstract

N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A), a cannabinoid CB1 receptor antagonist, has inverse agonist effects in cannabinoid CB1 receptor-expressing cell lines, brain and peripheral organs. These studies characterized SR141716A-inhibited G-protein activity by measuring [S-35]GTP gammaS binding. Maximal inhibition of basal [S-35]GTP gammaS binding in cerebellar membranes was 50%. The EC50 value for inhibition of [S-35]GTP gammaS binding was 4.4 muM, whereas the K-c for inhibition of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2)-stimulated [S-35]GTP gammaS binding was 0.6 nM.[S-35]GTP gammaS autoradiography was used to examine the regional specificity of SR141716A inhibition. SR141716A inhibited basal [S-35]GTP gammaS binding in all regions examined, with inhibition ranging from approximately 20% in caudate-putamen to 40% in hippocampus. These studies demonstrate that SR141716A is a competitive antagonist at nanomolar concentrations, whereas it inhibits basal receptor-mediated G-protein activity at micromolar concentrations. These data suggest that the apparent inverse agonist effect is either not cannabinoid CB1 receptor-specific or that SR141716A is binding to different sites on the cannabinoid CB1 receptor to produce inverse agonist versus competitive antagonist effects. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 08:23:57