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Titolo:
Allosteric modulation in spontaneously active mutant gamma-aminobutyric acid(A) receptors in frogs
Autore:
Findlay, GS; Ueno, S; Harrison, NL; Harris, RA;
Indirizzi:
Univ Texas, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA Univ Texas Austin TX USA 78712 Alcohol & Addict Res, Austin, TX 78712 USA Cornell Univ, Weill Med Coll, Dept Anesthesiol, New York, NY USA Cornell Univ New York NY USA ed Coll, Dept Anesthesiol, New York, NY USA
Titolo Testata:
NEUROSCIENCE LETTERS
fascicolo: 3, volume: 293, anno: 2000,
pagine: 155 - 158
SICI:
0304-3940(20001103)293:3<155:AMISAM>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GABA(A) RECEPTORS; GLYCINE RECEPTORS; ANESTHETIC ACTION; XENOPUS OOCYTES; POTENTIATION; ISOFLURANE; MUTATIONS; ETHANOL; ALCOHOL; SUBUNIT;
Keywords:
gamma-aminobutyric acid(A) receptor; mutagenesis; picrotoxin; bicuculline; pentobarbital; flunitrazepam; 5 alpha-pregnan-3 alpha-ol-20-one; allosteric modulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
14
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, RA Univ Texas, Waggoner Ctr Alcohol & Addict Res, A4800,2500 Speedway MBB1-124, Austin, TX 78712 USA Univ Texas A4800,2500 Speedway MBB1-124 Austin TX USA 78712 USA
Citazione:
G.S. Findlay et al., "Allosteric modulation in spontaneously active mutant gamma-aminobutyric acid(A) receptors in frogs", NEUROSCI L, 293(3), 2000, pp. 155-158

Abstract

Tryptophan substitutions were made in the second transmembrane domain of the gamma -aminobutyric acid(A) (GABAA) receptor alpha and beta subunits andthe resulting mutant receptors, containing alpha (2)(S270W) and/or beta (1)(S265W), were expressed in Xenopus oocytes. Mutation of either or both subunits resulted in receptors that exhibited enhanced sensitivity to agonist and were spontaneously active in the absence of GABA. The spontaneous activity was blocked by picrotoxin or bicuculline. The enhancement of GABA-induced currents by pentobarbital, by the neurosteroid 5 alpha -pregnan-3 alpha -ol-20-one, and by the benzodiazepine flunitrazepam was dramatically reduced in the mutant receptors. These results are consistent with the idea that a mutation that promotes gating behavior in a ligand-gated ion channel willalso show reduced effects of all positive allosteric modulators in a generalized manner, even when these modulators act at distinct sites on the receptor. (C) 2000 Published by Elsevier Science Ireland Ltd.

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Documento generato il 05/04/20 alle ore 03:47:56