Activation of protein kinase C attenuates the cyclic GMP responses to C-type natriuretic peptide in cultured mouse astrocytes.

C-type natriuretic peptide (CNP), a recently discovered natriuretic peptide, has a potent stimulatory effect on cyclic GMP (cGMP) formation in cultured mouse astrocytes. Pretreatment of astrocytes with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), attenuated CNP-induced cGMP responses in a dose-dependent manner, with a half-maximal inhibitory concentration of 6 nM, whereas the inactive phorbol ester analog, 4 alpha-phorbol 12,13-didecanoate, was without effect. In the presence of staurosporine, a PKC inhibitor, the inhibitory effect of PMA on CNP-stimulated cGMP production was reversed. These results suggest that PKC is an inhibitory modulator of CNP-stimulated cGMP responses in astrocytes and that CNP may interact with neuropeptides which stimulate PKC.