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Titolo:
Essential role of extracellular charged residues of the human CCK1 receptor for interactions with SR 146131, SR 27897 and CCK-8S
Autore:
Gouldson, P; Legoux, P; Carillon, C; Dumont, X; Le Fur, G; Ferrara, P; Shire, D;
Indirizzi:
Sanofi Synthelabo, Ctr Labege, F-31676 Labege, France Sanofi Synthelabo Labege France F-31676 r Labege, F-31676 Labege, France
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 2-3, volume: 389, anno: 2000,
pagine: 115 - 124
SICI:
0014-2999(20000218)389:2-3<115:EROECR>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHOLECYSTOKININ-A RECEPTOR; 3 DIFFERENT STATES; FUNCTIONAL EXPRESSION; DIRECT IDENTIFICATION; PANCREATIC ACINI; AFFINITY; PROTEIN; BINDING; AGONIST; DOMAINS;
Keywords:
cholecystokinin CCK1; receptor; mutagenesis; charged residue; SR 27897; SR 146131;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Gouldson, P Sanofi Synthelabo, Ctr Labege, Labege Innopole Voie 1,BP 137, F-31676 Labege, France Sanofi Synthelabo Labege Innopole Voie 1,BP 137 Labege France F-31676
Citazione:
P. Gouldson et al., "Essential role of extracellular charged residues of the human CCK1 receptor for interactions with SR 146131, SR 27897 and CCK-8S", EUR J PHARM, 389(2-3), 2000, pp. 115-124

Abstract

We hypothesized that charge-charge interactions may be important for the binding of the human cholecystokinin type 1 (CCK1) receptor-specific non-peptide full agonist SR 146131, (2-[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexyl-ethyl)-thiazol-2-ylcarbamoyl]-5,7-dimethyl-indol-1-yl-1-acetic acid), the competitive antagonist SR 27897, (1-[2-(4-(2-chlorophenyl)thiazol-2-yl) aminocarbonyl indoyl] acetic acid) and the natural octapeptide CCK-8S tothe CCK1 receptor. Alanine replacement studies of positively charged residues in the extracellular domains of the receptor showed that only the R336Amutation affected SR 146131 potency of mutated receptors transiently expressed in monkey kidney epithelial COS-7 cells. Two residues, Lys(115) and Lys(187), were implicated in SR 27897 binding. Only the replacement of Lys(115), Arg(197) and Arg(336) significantly affected CCK-8S binding or activity. These results clearly indicated the importance of certain charged residues, but not others, in SR 146131, SR 27897 and CCK-8S binding. Furthermore, although these molecules probably occupy different binding sites on the CCK1 receptor, we show that a small non-peptide agonist, SR 146131, can stimulate the dual signaling pathways mediated by the CCK1 receptor. (C) 2000 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 15/07/20 alle ore 20:42:56