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.
Yeung
V T
VT
Department of Medicine, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT.
Ho
S K
SK
Cockram
C S
CS
Lee
C M
CM
Nicholls
M G
MG
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D051379:Mice; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate