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Titolo:
Effects of varying the expression level of recombinant human mGlu1 alpha receptors on the pharmacological properties of agonists and antagonists
Autore:
Hermans, E; Challiss, RAJ; Nahorski, SR;
Indirizzi:
Univglandester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, En Univ Leicester Leicester Leics England LE1 9HN icester LE1 9HN, Leics, En
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 4, volume: 126, anno: 1999,
pagine: 873 - 882
SICI:
0007-1188(199902)126:4<873:EOVTEL>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOTROPIC GLUTAMATE RECEPTORS; PHENYLGLYCINE DERIVATIVES; PHOSPHOINOSITIDE TURNOVER; INDUCIBLE EXPRESSION; MGLUR1; CELLS; SUBTYPES; 1-ALPHA; ACTIVATION; RESPONSES;
Keywords:
type 1 alpha metabotropic glutamate receptor; phosphoinositide turnover; inositol 1,4,5-trisphosphate; LacSwitch; receptor induction; IPTG; inducible expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Hermans, E Univ Catholique Louvain, Pharmacol Lab, 54 Ave Hippocrate, B-1200 Brussels, Univ Catholique Louvain 54 Ave Hippocrate Brussels Belgium B-1200
Citazione:
E. Hermans et al., "Effects of varying the expression level of recombinant human mGlu1 alpha receptors on the pharmacological properties of agonists and antagonists", BR J PHARM, 126(4), 1999, pp. 873-882

Abstract

1 Different expression levels of the human type Ice metabotropic glutamate(mGlu1 alpha) receptor were obtained in transfected Chinese hamster ovary cells using an isopropyl beta-D-thiogalactopyranoside (IPTG) inducible system. Expression of mGlu1 alpha receptors could not be detected using immunoblotting or immunocytochemical approaches in non-induced cells, however, controlled expression could be induced following IPTG addition in a time- and concentration-dependent manner.2 In induced cells (100 mu M IPTG, 20 h) the agonists L-quisqualate or 1-aminocyclopentane-1S,3R-dicarboxylic acid stimulated large increases in [H-3]-inositol (poly)phosphate (in the presence of Lif) and inositol, 1,4,5-trisphosphate levels.3 Induction with 1-100 mu M IPTG allowed the receptor density to be increased incrementally and this not only resulted in an increase in the maximum response to. L-quisqualate, 1-aminocyclopentane-1S,3R-dicarboxylic acid and(S)-3,5-dihydroxy-phenylglycine, but also in an increase in the respectivepotencies of each agent to activate phosphoinositide hydrolysis.4 The intrinsic activity of the partial agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid dramatically increased with increasing receptor expression.5 The activities of the competitive mGlu1 alpha receptor antagonists (S)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxy-3-hydroxyphenylglycinefor inhibition of the effects of L-quisqualate or (S)3,5-dihydroxyphenylglycine were found to be independent of the receptor expression level.6 When the mGlu1 alpha receptor was expressed at very high levers, no evidence for receptor constitutive activity could be detected, and none of the antagonists tested revealed either any intrinsic activity or negative efficacy.7 These data demonstrate that both the potency and efficacy of mGlu1 alpha: receptor agonists are influenced by expression level, whilst mGlu1 alpha receptor antagonist activities are independent of expression level.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 21:53:06