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Titolo:
Agonist activation and alpha-bungarotoxin inhibition of wild type and mutant alpha 7 nicotinic acetylcholine receptors
Autore:
Kempsill, FEJ; Covernton, PJO; Whiting, PJ; Connolly, JG;
Indirizzi:
Univ Strathclyde, Dept Physiol & Pharmacol, Strathclyde Inst Biomed Sci, Glasgow G4 0NR, Lanark, Scotland Univ Strathclyde Glasgow Lanark Scotland G4 0NR G4 0NR, Lanark, Scotland Merck Sharp & Dohme Res Labs, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England Merck Sharp & Dohme Res Labs Harlow Essex England CM20 2QR Essex, England
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 383, anno: 1999,
pagine: 347 - 359
SICI:
0014-2999(19991103)383:3<347:AAAAIO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOLOGICAL PROPERTIES; CHANNEL DOMAIN; BINDING-SITE; STRUCTURAL DETERMINANTS; HIPPOCAMPAL-NEURONS; XENOPUS-OOCYTES; AMINO-ACIDS; CELL-LINES; SUBUNIT; MUTATIONS;
Keywords:
oocytes; nicotinic; receptor; alpha 7; alpha-bungarotoxin; mutagenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Kempsill, FEJ Univ Strathclyde, Dept Physiol & Pharmacol, Strathclyde InstBiomed Sci, 27 Taylor St, Glasgow G4 0NR, Lanark, Scotland Univ Strathclyde 27 Taylor St Glasgow Lanark Scotland G4 0NR
Citazione:
F.E.J. Kempsill et al., "Agonist activation and alpha-bungarotoxin inhibition of wild type and mutant alpha 7 nicotinic acetylcholine receptors", EUR J PHARM, 383(3), 1999, pp. 347-359

Abstract

The properties of wild type and mutant rat nicotinic alpha 7 receptors expressed in Xenopus oocytes were investigated using electrophysiology and site-directed mutagenesis. When compared at individual agonist concentrations,neither the normalised nicotinic, nor acetylcholine, responses of the wildtype receptors were significantly different from the corresponding responses obtained from a first extracellular domain mutant, phenylalanine(189) tyrosine (P > 0.05). The dissociation constants (K-D) of the wild type (4.7 nM) and Phe(189)Tyr mutant (5.2 nM) receptors for alpha-bungarotoxin were estimated by an electrophysiological approach. The similarity of the results suggests that the mutation did not lead to a widespread disruption of structure-function relationships, although a slight change in nicotine sensitivity may have occurred. In contrast, the mutations (Tyr(190)Gln, first extracellular domain), (Glu(261)Ala, M2 region) severely compromised receptor function. An additional mutation was made in a negatively charged motif of thesecond extracellular domain which is conserved in homomeric nicotinic receptors. This mutation, Asp(268)Ala, also caused a loss of function. Thus thestructure-function relationships in nicotinic alpha 7 receptors have parallels with heteromeric nicotinic receptors, but there may also be some marked differences. (C) 1999 Elsevier Science B.V. All rights reserved.

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Documento generato il 01/10/20 alle ore 02:50:29