Mechanism of c-type natriuretic peptide neuromodulation: Involvement of anp-c receptor, phospholipase c and protein kinase c

C-type natriuretic peptide (CNP) reduces depolarization induced catecholamine release from rat differentiated pheochromocytoma (PC12) cells. The maximal reduction of K⁺ evoked dopamine release is 31 ± 11 % at a CNP concentration of 10 nM. We tested the involvement of the ANP-C receptor, Phospholipase C (PLC) and protein kinase C (PKC) as potential signal transducing molecules in the neuromodulatory effects of CNP. CNP suppressed calcium (10 uM) stimulated 1,2-diacylglycerol (DAG) generation maximally by 34 ± 5% at a concentration of 10 nM. cANF, a truncated analog of Atrial natriuretic peptide that selectively binds the ANP-C receptor, mimicked the effects of CNP on DAG generation. Reduction of calcium stimulated DAG production averaged 91+2 % in the presence of 100 nM cANF. DAG is an activator of PKC which potentiates catecholamine release. In the presence of staurosporine, an inhibitor of PKC, CNP's effects on catecholamine release were completely abolished. These results suggest a role for the ANP-C receptor, PLC and PKC as intermediary molecules in CNP's effects on catecholamine release reduction.