Abstract

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 production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]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 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)