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Titolo:
M(2)-MUSCARINIC RECEPTORS - HOW DOES LIGAND-BINDING AFFINITY RELATE TO INTRINSIC ACTIVITY
Autore:
VANGELDEREN JG; DAEFFLER L; SCHERRER D; MOUSLI M; LANDRY Y; GIES JP;
Indirizzi:
UNIV LOUIS PASTEUR STRASBOURG 1,INSERM U425,LAB NEUROIMMUNOPHARMACOL,BP 24 F-67401 ILLKIRCH GRAFFENS FRANCE UNIV LOUIS PASTEUR STRASBOURG 1,INSERM U425,LAB NEUROIMMUNOPHARMACOL F-67401 ILLKIRCH GRAFFENS FRANCE
Titolo Testata:
Journal of receptor and signal transduction research
fascicolo: 1-2, volume: 16, anno: 1996,
pagine: 135 - 148
SICI:
1079-9893(1996)16:1-2<135:MR-HDL>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENYLATE-CYCLASE; G-PROTEINS; AGONIST; ACTIVATION; HETEROGENEITY; FREQUENCY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
18
Recensione:
Indirizzi per estratti:
Citazione:
J.G. Vangelderen et al., "M(2)-MUSCARINIC RECEPTORS - HOW DOES LIGAND-BINDING AFFINITY RELATE TO INTRINSIC ACTIVITY", Journal of receptor and signal transduction research, 16(1-2), 1996, pp. 135-148

Abstract

In this study we looked for evidence regarding a correlation between M(2)-muscarinic receptor binding affinity and ligand intrinsic activity. Guanine nucleotide-binding protein-coupled receptors have been shown to exist in both a high affinity and a low affinity, agonist state. The agonist [H-3]Oxotremorine-M, was used to determine the affinity ofcompounds for the high affinity state and the antagonist, [H-3]N-methylscopolamine, plus GppNHp, was used to determine the affinity for thelow agonist state. The magnitude of the difference in the affinity a compound has for the high versus the low agonist state of the receptorhas been related to the intrinsic activity of the compound. NMS/Oxo-Mratios were established for muscarinic agonists, partial agonists andantagonists. NMS/Oxo-M ratios varied from 1695 for the agonist carbachol to 1.9 for the antagonist AFDX-116 with intermediate values for the partial agonists oxotremorine-M, pilocarpine and RS86 (233, 36 and 17 respectively). Intrinsic activity was assessed by receptor-mediated G(i)-protein GTPase activity. Indeed, a close correlation (r=0.92) wasfound between the NMS/Oxo-M ratios of the ligands on the one hand, and their ability to activate the M(2)-receptor coupled G(i)-protein on the other.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/10/20 alle ore 10:31:16