title: GTP and Na+ modulate receptor-adenyl cyclase coupling and receptor-mediated function.
abstract: 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.
mesh_terms: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D004789:Enzyme Activation; D004912:Erythrocytes / Q000201:enzymology; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate / Q000502:physiology*; D006801:Humans; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism; D012156:Reticulocytes / Q000201:enzymology; D012964:Sodium / Q000502:physiology*; D010566:Virulence Factors, Bordetella
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002352:Carrier Proteins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D012964:Sodium; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases