Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
1999 Jun 01;1273:601-4. doi: 10.1038/sj.bjp.0702611.
Show Gene links
Show Anatomy links
A single amino acid confers barbiturate sensitivity upon the GABA rho 1 receptor.
Belelli D
,
Pau D
,
Cabras G
,
Peters JA
,
Lambert JJ
.
???displayArticle.abstract???
Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABAA receptor. By contrast, GABA receptors composed of the rho 1 subunit are anaesthetic-insensitive. Here, we demonstrate that both delta-hexachlorocyclohexane (delta-HCH; 1-100 microM), a positive allosteric modulator of the GABAA receptor, and the anaesthetic pentobarbitone (10-600 microM) have no effect on GABA-evoked currents mediated by wild-type rho 1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a rho 1 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 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action.
Amin,
Homomeric rho 1 GABA channels: activation properties and domains.
1994,
Pubmed
,
Xenbase
Barnard,
International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.
1998,
Pubmed
Belelli,
Interaction of positive allosteric modulators with human and Drosophila recombinant GABA receptors expressed in Xenopus laevis oocytes.
1996,
Pubmed
,
Xenbase
Belelli,
Modulation of human recombinant GABAA receptors by pregnanediols.
1996,
Pubmed
,
Xenbase
Belelli,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997,
Pubmed
,
Xenbase
Franks,
Molecular and cellular mechanisms of general anaesthesia.
1994,
Pubmed
Krasowski,
Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane.
1998,
Pubmed
Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1987,
Pubmed
Mair,
Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
McGurk,
The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor.
1998,
Pubmed
,
Xenbase
Mihic,
Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics.
1996,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Pistis,
Complementary regulation of anaesthetic activation of human (alpha6beta3gamma2L) and Drosophila (RDL) GABA receptors by a single amino acid residue.
1999,
Pubmed
,
Xenbase
Shimada,
gamma-Aminobutyric acid A or C receptor? gamma-Aminobutyric acid rho 1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive gamma-aminobutyric acid responses in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Woodward,
Effects of hexachlorocyclohexanes on gamma-aminobutyric acid receptors expressed in Xenopus oocytes by RNA from mammalian brain and retina.
1992,
Pubmed
,
Xenbase
Wooltorton,
Pharmacological and physiological characterization of murine homomeric beta3 GABA(A) receptors.
1997,
Pubmed
,
Xenbase