INHIBITION OF ADENYLYL-CYCLASE BY G(I-ALPHA)

Evidence suggests that both alpha and betagamma subunits of heterotrim eric guanine nucleotide-binding regulatory proteins (G proteins) inhib it adenylyl cyclase. Although type I adenylyl cyclase is inhibited dir ectly by exogenous betagamma, inhibition of adenylyl cyclase by G(ialp ha) has not been convincingly demonstrated in vitro. Concentration-dep endent inhibition of adenylyl cyclases by purified G(ialpha) subunits is described. Activated G(ialpha) but not G(oalpha) was effective, and myristoylation of G(ialpha) was required. The characteristics of the inhibitory effect were dependent on the type of adenylyl cyclase and t he nature of the activator of the enzyme. The concentrations of G(ialp ha) required to inhibit adenylyl cyclase were substantially higher tha n those normally thought to be relevant physiologically. However, anal ysis indicates that these concentrations may be relevant and reasonabl e.