A single amino acid confers barbiturate sensitivity upon the GABA ρ1 receptor

Delia Belelli (Lead / Corresponding author), Davide Pau, Giulia Cabras, John A. Peters, Jeremy J. Lambert

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABA(A) receptor. By contrast, GABA receptors composed of the ρ1 subunit are anaesthetic-insensitive. Here, we demonstrate that both δ-hexachlorocyclohexane (δ-HCH; 1-100 μM), a positive allosteric modulator of the GABA(A) receptor, and the anaesthetic pentobarbitone (10-600 μM) have no effect on GABA-evoked currents mediated by wild-type ρ1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a ρ1 receptor in which a transmembrane located isoleucine residue is replaced by serine. However, not all general anaesthetics were similarly influenced by this mutation, because propofol and 5β-pregnan-3α-ol-20-one (5β3α) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action.

Original languageEnglish
Pages (from-to)601-604
Number of pages4
JournalBritish Journal of Pharmacology
Volume127
Issue number3
DOIs
Publication statusPublished - Jun 1999

Fingerprint

General Anesthetics
GABA Receptors
GABA-A Receptors
Amino Acids
gamma-Aminobutyric Acid
Anesthetics
Lindane
Isoleucine
Xenopus laevis
Propofol
Pentobarbital
Synaptic Transmission
Serine
Oocytes
Central Nervous System
Mutation
barbituric acid

Keywords

  • δ-hexachlorocyclohexane
  • ρ-subunit
  • GABA(A) receptor
  • General anaesthetic
  • Pentobarbitone

Cite this

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title = "A single amino acid confers barbiturate sensitivity upon the GABA ρ1 receptor",
abstract = "Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABA(A) receptor. By contrast, GABA receptors composed of the ρ1 subunit are anaesthetic-insensitive. Here, we demonstrate that both δ-hexachlorocyclohexane (δ-HCH; 1-100 μM), a positive allosteric modulator of the GABA(A) receptor, and the anaesthetic pentobarbitone (10-600 μM) have no effect on GABA-evoked currents mediated by wild-type ρ1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a ρ1 receptor in which a transmembrane located isoleucine residue is replaced by serine. However, not all general anaesthetics were similarly influenced by this mutation, because propofol and 5β-pregnan-3α-ol-20-one (5β3α) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action.",
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A single amino acid confers barbiturate sensitivity upon the GABA ρ1 receptor. / Belelli, Delia (Lead / Corresponding author); Pau, Davide; Cabras, Giulia; Peters, John A.; Lambert, Jeremy J.

In: British Journal of Pharmacology, Vol. 127, No. 3, 06.1999, p. 601-604.

Research output: Contribution to journalArticle

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