Structure and function of cerebral GABAA and GABAB receptors.

The receptor for GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter in the brain, has been classified into GABAA and GABAB types. The GABAA receptor was purified by means of affinity column chromatography using benzodiazepine as an immobilized ligand. The results indicated that the GABAA receptor consists of several subunits and forms a GABA-gated Cl- channel, which is coupled with the benzodiazepine receptor. The molecular weight of the GABAA receptor complex was estimated to be approximately 300 kDa. Furthermore, cDNA cloning of GABAA receptor subunits was performed and the primary structure of these subunits was deduced. The results suggested that these subunits possess four transmembrane domains in their structure which are important for the formation of the Cl- channel. On the other hand, activation of GABAB receptors induced the inhibition of adenylyl cyclase activity and phosphatidylinositol turnover via inhibitory GTP-binding proteins such as G(i) and/or G(o). The GABAB receptor was purified using baclofen affinity and immunoaffinity column chromatographies. It was confirmed that the purified GABAB receptor protein is about 80 kDa in its molecular weight. This protein is capable of inducing the inhibition of adenylyl cyclase when it is reconstituted with G(i)/G(o) protein in the phospholipid vesicle system. Currently available data indicate that GABAA and GABAB receptors in the central nervous system are distinct not only in terms of their molecules but also their signal transduction systems. However, the primary structure and synaptic localization of GABAB receptor molecules in the brain remain to be clarified.