GTP and Na+ modulate receptor-adenyl cyclase coupling and receptor-mediated function.

Activation and inhibition of adenylate cyclase activity is mediated via two distinct GTP-binding proteins. In both stimulatory and inhibitory systems, receptor occupancy by a hormone or agonist drug stabilizes receptor interactions with its functionally associated GTP-binding protein and, as a consequence, facilitates GTP occupancy of the regulatory protein. Activation of cyclase proceeds until GTP is hydrolyzed to GDP. Although hormonal inhibition of cyclase is elicited by a sequence of molecular events seemingly parallel to those for activation of cyclase, it is not known whether hormonal inhibition of cyclase involves the direct interaction of the GTP-occupied inhibitory regulatory protein with the catalytic subunit or results indirectly from destabilization of the interaction of the stimulatory GTP-binding protein with the catalytic moiety. Sodium ion also modulates receptor-mediated inhibition of adenylate cyclase, although apparently via a component distinct from the GTP-binding subunit of the inhibitory GTP-binding protein. Sodium also influences the physiological functions elicited by receptors that mediate inhibition of cyclase, at least for alpha 2-adrenergic-promoted platelet secretion. The relationship between sodium effects on hormonal attenuation of cAMP accumulation and elicited physiological effects is discussed.