SEQUENCE AND REGIONAL DISTRIBUTION OF THE MESSENGER-RNA ENCODING THE ALPHA-2-POLYPEPTIDE OF RAT GAMMA-AMINOBUTYRIC ACIDA RECEPTORS

A cDNA from a rat hippocampal cDNA library encodes an isoform of the alpha polypeptide of the gamma-aminobutyric acid (GABA)/benzodiazepine (BZ) receptor. Its deduced amino acid sequence is 96% identical to that of the alpha-2 polypeptide of the bovine GABA(A) receptor. The polypeptide has features shared by all previously reported GABA(A) receptor alpha polypeptides and shares 71-76% identity with previously described rat alpha polypeptides. Most of the differences lie in the presumed extracellular and intracellular domains. On Northern blots, the alpha-2 cDNA detects two mRNAs, which are found in cortex, hippocampus and striatum, brain regions enriched in pharmacologically defined "BZ type II" receptors. Other workers have previously shown that the alpha polypeptides of the GABA(A) receptor largely determine the BZ binding properties of reconstituted receptors. The distribution of alpha-2 mRNAs in rat brain suggests that the alpha-2 subunit may indeed be involved in the BZ type II receptors.