Journal article
Sites of alcohol and volatile anaesthetic action on GABA A and glycine receptors
Nature (London), Vol.389(6649), pp.385-389
09/25/1997
DOI: 10.1038/38738
PMID: 9311780
Abstract
Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as γ-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABAA and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA ρ1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABAA and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.
Details
- Title: Subtitle
- Sites of alcohol and volatile anaesthetic action on GABA A and glycine receptors
- Creators
- Suzanne E Finn - Departments of Anesthesia and Critical Care, The University of ChicagoMarilee J Wick - Department of Pharmacology, University of Colorado Health Sciences Center Denver Veteran Administration Medical Center, Alcoholism Research CenterMaria Paola Mascia - Department of Pharmacology, University of Colorado Health Sciences CenterEric P Greenblatt - Department of Anesthesia, University of PennsylvaniaR. Adron Harris - Department of Pharmacology, University of Colorado Health Sciences Center Denver Veteran Administration Medical Center, Alcoholism Research Center Departments of Pharmacological and Physiological Sciences, The University of ChicagoMatthew D Krasowski - Departments of Neurobiology, The University of ChicagoS. John Mihic - Department of Pharmacology, University of Colorado Health Sciences Center Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest UniversityC. Fernando Valenzuela - Department of Pharmacology, University of Colorado Health Sciences CenterKirsten K Hanson - Departments of Anesthesia and Critical Care, The University of ChicagoVladimir V Koltchine - Departments of Pharmacological and Physiological Sciences, The University of ChicagoNeil L Harrison - Departments of Anesthesia and Critical Care, The University of Chicago Departments of Pharmacological and Physiological Sciences, The University of Chicago Departments of Neurobiology, The University of ChicagoQing Ye - Departments of Anesthesia and Critical Care, The University of Chicago
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.389(6649), pp.385-389
- DOI
- 10.1038/38738
- PMID
- 9311780
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 09/25/1997
- Academic Unit
- Pathology
- Record Identifier
- 9984047717802771
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