Role of the beta subunit in determining the pharmacology of human gamma- aminobutyric acid type A receptors [published erratum appears in Mol Pharmacol 1994 Jul;46(1):211]

KL Hadingham, PB Wingrove, KA Wafford, C Bain, JA Kemp, KJ Palmer, AW Wilson, AS Wilcox, JM Sikela and CI Ragan

Merck Sharp & Dohme Research Laboratories, Harlow, Essex, England.

A cDNA encoding the human gamma-aminobutyric acid (GABA)A receptor beta 2 subunit has been cloned and sequenced. The deduced amino acid sequence of this cDNA shows only a single amino acid change from the rat sequence (Asn-347 in rat, serine in human). Using polymerase chain reaction amplification of human-specific products from human x rodent somatic cell hybrid DNAs, the gene has been assigned to human chromosome 6. By expressing recombinant human GABAA receptors containing different beta subunits (beta 1, beta 2 or beta 3) in both transfected cells and Xenopus oocytes, we have been able to determine the influence of the beta subunit on the pharmacology of the receptor. For a number of benzodiazepine binding site compounds, a barbiturate, and several neurosteroids, neither the affinity nor the efficacy of the compounds is influenced by the type of beta subunit present in the receptor molecule. These data suggest that the beta subunit does not significantly influence the benzodiazepine, barbiturate, or steriod site pharmacologies of human GABAA receptor subtypes.

Volume 44, Issue 6, pp. 1211-1218, 12/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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