Natriuretic peptides suppress protein kinase C activity to reduce evoked dopamine efflux from pheochromocytoma (PC12) cells.
The observation that natriuretic peptides and protein kinase C activators influence evoked neurotransmitter efflux by diametrically opposed mechanisms prompted an investigation of the influence of natriuretic peptides on protein kinase C activity and the potential involvement of this pathway in neuromodulatory responses to natriuretic peptides. C-Type natriuretic peptide attenuated both evoked dopamine efflux and protein kinase C activity in a concentration-dependent manner consistent with a 10% diminution in protein kinase C activity producing a 4.6-6.2% reduction in evoked dopamine efflux. The ability of C-type natriuretic peptide to suppress evoked dopamine efflux was abolished by treatment with the protein kinase C inhibitors chelerythrine (10 micro M) and staurosporine (10 nM). Both chelerythrine and staurosporine attenuated protein kinase C activity at the concentrations used. The natriuretic peptide C receptor (NPR-C) appeared to mediate the attenuation of protein kinase C activity, because the effect was mimicked by a pentadecapeptide fragment of the NPR-C, and the effect of C-type natriuretic peptide was attenuated by an antibody generated against the same region of the receptor. These data suggest that C-type natriuretic peptide attenuates neurotransmitter efflux by a mechanism involving suppression of neuronal protein kinase C activity via an interaction with the NPR-C.
Trachte
George J
GJ
Department of Pharmacology, University of Minnesota-Duluth School of Medicine, Duluth, Minnesota 55812, USA. gtracht1@d.umn.edu
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D004298:Dopamine / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000502:physiology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D016716:PC12 Cells / Q000201:enzymology / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D010617:Phenanthridines; D020098:Natriuretic Peptide, C-Type; C016299:chelerythrine; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D019311:Staurosporine; D004298:Dopamine