We studied the selectivity of GABAB receptors for coupling to G proteins by testing the ability of various purified G proteins to increase GABA binding to N-ethylmaleimide (NEM)-treated membranes of bovine brain. The addition of Go, G∗ o or gi1 to NEM-treated membranes increased GABA binding in a dose-dependent manner. However, the addition of Gi2 did not elicit a marked increase in GABA binding. When α subunits of G proteins were mixed with various brain βγ subunit complexes composed of different γ subunits, and they were added to the NEM-treated membranes, Gi2 with any βγ subunits hardly increased GABA binding. On the other hand, Go with any βγ subunits caused a marked increase, though Go with a small γ subunit was more effective than that with a large γ subunit. These data suggest that the selective coupling of the G proteins to GABAB receptors is determined by the α subunit.
