Activation and inhibition of adenylate cyclase by hormones: mechanistic aspects

Eucaryotic adenylate cyclases are coupled to hormone and neurotransmitter receptors in two modes: stimulatory and inhibitory. Stimulation of cyclase by agonist requires the presence of GTP at a concentration range of 0.01-0.10 μM. Hormone-induced inhibition of adenylate cyclase requires GTP at a concentration range of 0.2-6.0 μM. The possible modes of coupling between the stimulatory receptor, the GTP regulatory protein and the catalytic unit have been examined in the light of accumulating experimental data. It is concluded that the main event in the activation of enzyme is the bimolecular encounter between the agonist-receptor complex and the complex between the GTP regulatory site and the catalytic moiety. An analysis of existing knowledge about the mode of inhibition of adenylate cyclase by hormones suggests that the inhibitory hormone functions through a separate GTP binding site from the catalytic site.