The α(2A)-adrenergic receptor discriminates between G(i) heterotrimers of different βγ subunit composition in Sf9 insect cell membranes

Abstract

In view of the expanding roles of the βγ subunits of the G proteins in signaling, the possibility was raised that the rich diversity of βγ subunit combinations might contribute to the specificity of signaling at the level of the receptor. To test this possibility, Sf9 cell membranes expressing the recombinant α(2A)-adrenergic receptor were used to assess the contribution of the βγ subunit composition. Reconstituted coupling between the receptor and heterotrimeric G(i) protein was assayed by high affinity, guanine nucleotide-sensitive binding of the α2-adrenergic agonist, [3H]UK-14,304. Supporting this hypothesis, the present study showed clear differences in the abilities of the various βγ dimers, including those containing the β3 subtype and the newly described γ4, γ10, and γ11 subtypes, to promote interaction of the same α(i) subunit with the α(2A)-adrenergic receptor.