γ-アミノ酪酸(GABA)受容体の構造と機能: 研究の現況とその問題点

抄録

The γ-aminobutyric acid (GABA) receptor has been classified into two receptor subtypes (GABA_A and GABAA_B receptors) based on their pharmacological properties. The GABAA_A receptor in the central nervous system (CNS) has been found to be coupled structurally as well as functionally with the benzodiazepine receptor and Cl- channel. Purified GABAA_A receptor from bovine brain consisted of both α and β subunits. The complementary DNA_S encoding the GABAA_A receptor α and β subunits have been cloned; and from their elucidated nucleotide sequences, the amino acid sequences of the subunits were deduced. The structure of both subunits, having four putative membrane domains, has been found to be similar to other ligand-gated receptors such as the nicotinic acetylcholine receptor α subunit and glycine receptor 48K subunit. Therefore, it has been suggested that these ligand-gated receptors comprise a superfamily. In addition, the presence of similarities in the nucleotide and deduced amino acid sequences of human brain GABAA_A receptor with those of bovine brain has been noted. On the other hand, the GABA_B receptor, which is insensitive to bicuculline but sensitive to baclofen, has been found to be pharmacologically distinct from the GABAA_A receptor. The GABA_B receptor in the brain has been found to be coupled with GTP-binding protein and generates the inhibitory transmission coupled with various intracellular effector systems such as adenylate cyclase and phosphoinositides turnover. The exact structure and function of the GABA_B receptor in the CNS, however, remain to be clarified in future studies.