Down-regulation of protein kinase C potentiates atrial natriuretic peptide-stimulated cGMP accumulation in vascular smooth-muscle cells.
It has been reported that atrial natriuretic peptide (ANP) produces inositol phosphates and diacylglycerol in vascular smooth muscle cells (VSMC). The purpose of this study is to investigate whether diacylglycerol produced by ANP affects ANP-induced cyclic GMP (cGMP) accumulation through the activation of protein kinase C. Short-term (15 min) treatment of rat aortic VSMC with protein kinase C activating phorbol 12-myristate 13-acetate (PMA, 100 nM) decreased ANP (100 nM)-induced cGMP accumulation by 34.7% in the presence of IBMX (0.5 mM). However, the long-term (24 h) treatment to decrease the activity of protein kinase C led to an enhancement of the cGMP accumulation by 69.6% compared with that of control VSMC. There were no significant differences in Bmax and Kd for ANP and ANP-dependent particular guanylyl cyclase activity between long-term PMA-treated and control VSMC. In the present study, we show that the activation of protein kinase C attenuates the cGMP accumulation induced by ANP and that down-regulation of protein kinase C results in an enhancement of the cGMP accumulation. These data are consistent with the role of protein kinase C as a negative regulator in ANP-receptor/guanylyl cyclase pathway.
First Department of Internal Medicine, Asahikawa Medical College, Japan.
J
J
Kawabe
Y
Y
Ohsaki
S
S
Onodera
D000818:Animals; D001011:Aorta; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010446:Peptide Fragments; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; C062522:atrial natriuretic factor prohormone (103-123); D011493:Protein Kinase C; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate