ROLE OF THE BETA-SUBUNIT IN DETERMINING THE PHARMACOLOGY OF HUMAN GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTORS

A cDNA encoding the human gamma-aminobutyric acid (GABA)A receptor bet a2 subunit has been cloned and sequenced. The deduced amino acid seque nce of this cDNA shows only a single amino acid change from the rat se quence (Asn-347 in rat, serine in human). Using polymerase chain react ion amplification of human-specific products from human x rodent somat ic cell hybrid DNAs, the gene has been assigned to human chromosome 6. By expressing recombinant human GABA(A) receptors containing differen t beta subunits (beta1, beta2, or beta3) 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 benz odiazepine binding site compounds, a barbiturate, and several neuroste roids, neither the affinity nor the efficacy of the compounds is influ enced by the type of beta subunit present in the receptor molecule. Th ese data suggest that the beta subunit does not significantly influenc e the benzodiazepine, barbiturate, or steroid site pharmacologies of h uman GABA(A) receptor subtypes.