Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Agonist efficacy at the alpha(2A)-adrenoceptor : G(alpha 15) fusion protein: an analysis based on Ca2+ responses
Autore:
Pauwels, PJ; Finana, F; Tardif, S; Colpaert, FC; Wurch, T;
Indirizzi:
Ctr Rech Pierre Fabre, Dept Cellular & Mol Biol, F-81106 Castres, France Ctr Rech Pierre Fabre Castres France F-81106 ol, F-81106 Castres, France
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 6, volume: 361, anno: 2000,
pagine: 672 - 679
SICI:
0028-1298(200006)361:6<672:AEATA:>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; GAMMA-S BINDING; ALPHA-2-ADRENERGIC RECEPTOR; ADRENERGIC-RECEPTORS; QUANTITATIVE-ANALYSIS; SIGNAL-TRANSDUCTION; ACTIVATION; MODULATION; MEMBRANES; MUTATION;
Keywords:
recombinant alpha(2A) AR and G(alpha 15) protein; fusion protein; Ca2+ response; ligand efficacy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Pauwels, PJ Ctr Rech Pierre Fabre, Dept Cellular & Mol Biol, 17 Ave Jean Moulin, F-81106 Castres, France Ctr Rech Pierre Fabre 17 Ave Jean Moulin Castres France F-81106
Citazione:
P.J. Pauwels et al., "Agonist efficacy at the alpha(2A)-adrenoceptor : G(alpha 15) fusion protein: an analysis based on Ca2+ responses", N-S ARCH PH, 361(6), 2000, pp. 672-679

Abstract

A fusion protein was constructed between the recombinant human alpha(2A)-adrenoceptor and a mouse G(alpha 15) protein to measure the efficacy of agonist-induced Ca2+ responses at a receptor:G(alpha 15) protein stoichiometry of 1. Activation of this fusion protein in CHO-K1 cells by (-)-adrenaline induced a time- and concentration-dependent (pE(50): 7.28 +/- 0.04) increasein the intracellular Ca2+ concentration. The magnitude of the Ca2+ response was related to the amount of the fusion protein and the number of surfacealpha(2A)-adrenoceptor binding sites as estimated by [H-3]RX 821002 binding. Whereas UK 14304 was as efficacious as (-)-adrenaline, the following ligands displayed partial agonist properties [E-max in percentage vs. (-)-adrenaline: d-medetomidine (76 +/- 3) > BHT 920 (53 +/- 3)> clonidine (39 +/- 4) >> oxymetazoline (10 +/- 1)]. This ligand activation profile was not affected over a 30-fold range of expression of the fusion protein in contrast to the observed enhancement of the partial agonists' maximal responses by co-expression of the alpha(2A)-adrenoceptol with increasing amounts of the G(alpha 15) protein. In conclusion, the fusion protein approach opens perspectives to quantify intrinsic activities of ligands under controlled experimental conditions of a fixed receptor:G(alpha 15) protein ratio of 1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 06:46:54