G-PROTEIN BETA-GAMMA-SUBUNITS INHIBIT PURIFIED ADENYLATE-CYCLASE INDEPENDENT OF THE ACTIVATION BY CA2+ AND CALMODULIN

Adenylate cyclase purified by affinity chromatography was activated ab out 2.5-fold in a Ca2+- and calmodulin-dependent fashion. G protein be tagamma-subunits, an inhibitor in the receptor-mediated inhibition of adenylate cyclase, inhibited the purified cyclase by more than 80%. Th e extent of betagamma-induced inhibition was not affected by the activ ation with Ca2+ and calmodulin. Moreover, the prior addition of the be tagamma-subunits to the cyclase did not prevent the subsequent activat ion of the enzyme by Ca2+ and calmodulin. We conclude that the betagam ma-subunits inhibit adenylate cyclase activity in a calmodulin-indepen dent mode.