The interaction of general anaesthetics and neurosteroids with GABA(A) and glycine receptors

D. Belelli; M. Pistis; J. A. Peters; J. J. Lambert

doi:10.1016/S0197-0186(99)00037-6

The interaction of general anaesthetics and neurosteroids with GABA(A) and glycine receptors

D. Belelli, M. Pistis, J. A. Peters, J. J. Lambert (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

72 Citations (Scopus)

Abstract

The positive allosteric effects of four structurally distinct general anaesthetics (propofol, pentobarbitone, etomidate and 5α-pregnan-3α-ol-20-one [5α3α]) upon recombinant GABA(A) (α₆β₃γ(2L)), invertebrate GABA (RDL) and glycine (α₁) receptors expressed in Xenopus laevis oocytes have been determined. Propofol and pentobarbitone enhanced agonist (GABA or glycine as appropriate)-evoked currents at GABA(A), glycine, and RDL receptors, whereas etomidate and 5α3α were highly selective for the GABA(A) receptor. Utilizing site-directed mutagenesis, we demonstrate that the nature of the interaction of propofol, pentobarbitone and etomidate (but not 5α3α) with mammalian and invertebrate ionotropic GABA receptors depends critically upon the nature of a single amino acid located in the second transmembrane region (TM2) of these receptors. These data are discussed in relation to the specificity of action of general anaesthetics. Copyright (C) 1999.

Original language	English
Pages (from-to)	447-452
Number of pages	6
Journal	Neurochemistry International
Volume	34
Issue number	5
DOIs	https://doi.org/10.1016/S0197-0186(99)00037-6
Publication status	Published - May 1999

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title = "The interaction of general anaesthetics and neurosteroids with GABA(A) and glycine receptors",

abstract = "The positive allosteric effects of four structurally distinct general anaesthetics (propofol, pentobarbitone, etomidate and 5α-pregnan-3α-ol-20-one [5α3α]) upon recombinant GABA(A) (α6β3γ(2L)), invertebrate GABA (RDL) and glycine (α1) receptors expressed in Xenopus laevis oocytes have been determined. Propofol and pentobarbitone enhanced agonist (GABA or glycine as appropriate)-evoked currents at GABA(A), glycine, and RDL receptors, whereas etomidate and 5α3α were highly selective for the GABA(A) receptor. Utilizing site-directed mutagenesis, we demonstrate that the nature of the interaction of propofol, pentobarbitone and etomidate (but not 5α3α) with mammalian and invertebrate ionotropic GABA receptors depends critically upon the nature of a single amino acid located in the second transmembrane region (TM2) of these receptors. These data are discussed in relation to the specificity of action of general anaesthetics. Copyright (C) 1999.",

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