Dual regulation of adenylate cyclase and guanylate cyclase: alpha 2-adrenergic signal transduction in adrenocortical carcinoma cells.
Isolated adrenocortical carcinoma cells of rat contain alpha 2- and beta-adrenergic receptors. When these cells are incubated with alpha 2-adrenergic agonists, there is a concentration-dependent increase of cyclic GMP that is blocked by the alpha 2-adrenergic antagonist yohimbine but not by the beta-antagonist propranolol. Concomitantly, both p-aminoclonidine (20 microM) and clonidine (100 microM), the alpha 2-adrenergic agonists, stimulate membrane guanylate cyclase activity. In calcium free medium there is no alpha 2-agonist-dependent increase in cyclic GMP. Isoproterenol, a beta-agonist, and forskolin cause an increase in cyclic AMP but not cyclic GMP. The cyclic AMP increase induced by isoproterenol is blocked by propranolol but not by yohimbine. Isoproterenol- and forskolin-dependent increases in cyclic AMP are inhibited by p-aminoclonidine and the inhibition is relieved by yohimbine. These results indicate a dual regulation of guanylate cyclase and adenylate cyclase by the alpha 2-receptor signal: guanylate cyclase is coupled to the receptor in a positive fashion, whereas adenylate cyclase is coupled in a negative fashion. Calcium is obligatory in the cyclic GMP-mediated response.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP