C-TYPE NATRIURETIC PEPTIDE STIMULATES CATECHOLAMINE SYNTHESIS THROUGHTHE ACCUMULATION OF CYCLIC-GMP IN CULTURED BOVINE ADRENAL-MEDULLARY CELLS

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP produ ction induced by 1 mu M CNP reached a 200-fold increase, and the effec t of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 mu M ) and angiotensin II (0.1-1 mu M). 4) When the cells were cultured wit h hypertonic NaCl medium, the CNP-induced cyclic GMP production was po tentiated in a time (1-4 days)- and concentration (25-100 mM)-dependen t manner. 5) CNP stimulated the synthesis of C-14-labeled catecholamin es from [C-14]tyrosine but not from [C-14] dopa. The stimulatory effec t of CNP on the C-14-labeled catecholamine synthesis was observed at t he concentrations of 100 to 1000 nM. 6) 8-Bromo cyclic GMP, a membrane -permeable cyclic GMP analog, and sodium nitroprusside, an activator o f soluble guanylate cyclase, also stimulated the synthesis of'4Clabele d catecholamines from [C-14]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of C-14-labeled catecholami nes, 7)CNP (1 mu M) as well as 8-bromo cyclic GMP and sodium nitroprus side increased the activity of tyrosine hydroxylase in the cells. Thes e results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angioten sin II and the hypertonic NaCl condition. CNP may stimulate the catech olamine synthesis through the cyclic GMP-dependent activation of tyros ine hydroxylase in the adrenal medulla.