Inhibition of Adenylyl Cyclase by G iα

Abstract

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.