Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase.

Guanine Nucleotide-binding Regulatory Proteins and Dual Control of Adenylate Cyclase Investigation performed during the past five years has revealed that the hormone-sensitive adenylate cyclase system is far more complicated than originally suspected, consisting of at least three types of proteins embedded in the lipids of the plasma mem- brane. Receptors for a large number of hormones, neurotrans- mitters, and autacoids face the extracellular space and interact with appropriate endogenous ligands and with drugs. The in- teractions of such ligands with many types of receptors ultimately result in stimulation of adenylate cyclase activity, with resultant enhancement of intracellular phosphorylation as a consequence of the action of cyclic AMP-dependent protein kinases. Stim- ulatory receptors include those for,-adrenergic agonists, ad- renocorticotropic hormone, gonadotropins, and many others. Adenylate cyclase activity is also under inhibitory control by such agents as a2-adrenergic and muscarinic agonists and opioids; the ultimate physiological consequences ofthese inhibitory effects are somewhat less clear cut than are those that result from the stimulatory events.