Mutational analysis of molecular requirements for the actions of general anaesthetics at the γ-aminobutyric acidA receptor subtype, α1β2γ2Reportar como inadecuado




Mutational analysis of molecular requirements for the actions of general anaesthetics at the γ-aminobutyric acidA receptor subtype, α1β2γ2 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Pharmacology

, 3:13

First Online: 12 November 2003Received: 02 September 2003Accepted: 12 November 2003

Abstract

BackgroundAmino acids in the β subunit contribute to the action of general anaesthetics on GABAA receptors. We have now characterized the phenotypic effect of two β subunit mutations in the most abundant GABAA receptor subtype, α1β2γ2.

ResultsThe β2N265M mutation in M2 decreased the modulatory actions of propofol, etomidate and enflurane, but not of alphaxalone, while the direct actions of propofol, etomidate and alphaxalone were impaired. The β2M286W mutation in M3 decreased the modulatory actions of propofol, etomidate and enflurane, but not of alphaxalone, whereas the direct action of propofol and etomidate, but not of alphaxalone, was impaired.

ConclusionsWe found that the actions of general anaesthetics at α1β2N265Mγ2 and α1β2M286Wγ2 GABAA receptors are similar to those previously observed at α2β3N265Mγ2 and α2β3M286Wγ2 GABAA recpetors, respectively, with the notable exceptions that the direct action of propofol was decreased in α1β2M286Wγ2 receptors but indistinguishable form wild type in α2β3M286Wγ2 receptors and that the direct action of alphaxalone was decreased in α1β2N265Mγ2 but not α2β3N265Mγ2 receptors and indistinguishable form wild type in α1β2M286Wγ2 receptors but increased in α2β3M286Wγ2 receptors. Thus, selected phenotypic consequences of these two mutations are GABAA receptor subtype-specific.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-3-13 contains supplementary material, which is available to authorized users.

Roberta Siegwart, Karin Krähenbühl contributed equally to this work.

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Autor: Roberta Siegwart - Karin Krähenbühl - Sachar Lambert - Uwe Rudolph

Fuente: https://link.springer.com/







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