Inhibition of Adenylyl Cyclase by Giα

Evidence suggests that both α and βγ subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) inhibit adenylyl cyclase. Although type I adenylyl cyclase is inhibited directly by exogenous βγ, inhibition of adenylyl cyclase by G_iα has not been convincingly demonstrated in vitro. Concentration-dependent inhibition of adenylyl cyclases by purified G_iα subunits is described. Activated G_iα but not G_oα was effective, and myristoylation of G_iα was required. The characteristics of the inhibitory effect were dependent on the type of adenylyl cyclase and the nature of the activator of the enzyme. The concentrations of G_iα required to inhibit adenylyl cyclase were substantially higher than those normally thought to be relevant physiologically. However, analysis indicates that these concentrations may be relevant and reasonable.