Negative coupling of ?-aminobutyric acid (GABA)(B) receptor with phosphatidylinositol turnover in the brain.

Possible coupling between the ?-aminobutyric acid (GABA)(B) receptor, one of the GABA receptor subtypes, and phosphatidylinositol turnover, known to be a potent intracellular signal transducing system, has been examined in the rat brain. (?)Baclofen, an agonist of the GABA(B) receptor, significantly inhibited the accumulation of inositol-1-phosphate and inositol-1,4,5-triphosphate and these inhibitions were counteracted by the addition of phaclofen, a GABA(B) antagonist, as well as by treatment with islet-activating protein (IAP). These results suggest that the cerebral GABA(B) receptor may be coupled negatively with phosphatidylinositol turnover, and this negative coupling may also be mediated by the action of an IAP-sensitive GTP-binding protein.