GABAB receptors couple to G proteins Go, G∗o and G·i1 but not to Gi2

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, Go* 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 alpha subunits of G proteins were mixed with various brain beta gamma subunit complexes composed of different gamma subunits, and they were added to the NEM-treated membranes, Gi2 with any beta gamma subunits hardly increased GABA binding. On the other hand, Go with any beta gamma subunits caused a marked increase, though Go with a small gamma subunit was more effective than that with a large gamma subunit. These data suggest that the selective coupling of the G proteins to GABAB receptors is determined by the alpha subunit.