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 language | English |
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Pages (from-to) | 601-604 |
Number of pages | 4 |
Journal | British Journal of Pharmacology |
Volume | 127 |
Issue number | 3 |
DOIs | |
Publication status | Published - Jun 1999 |
Keywords
- δ-hexachlorocyclohexane
- ρ-subunit
- GABA(A) receptor
- General anaesthetic
- Pentobarbitone
ASJC Scopus subject areas
- Pharmacology