Protein kinase C inhibitors enhance endothelin-1 and attenuate vasopressin and angiotensin II evoked [Ca2+]i elevation in the rat cardiomyocyte.
Primary cultures of neonatal rat cardiomyocytes were pretreated for 16 h with either nonselective (staurosporine, 100 nM) or selective (NPC15437, 20 microM) protein kinase C (PKC) inhibitors. These inhibitors did not affect the basal cytosolic free calcium, [Ca2+]i, level (106 +/- 12 nM) as determined by fura-2 fluorescence methodology. Both agents significantly enhanced the maximal [Ca2+]i responses to endothelin-1 (ET-1) and attenuated the peak [Ca2+]i responses to arginine vasopressin and angiotensin II. They did not alter the EC50 values of any of these agonists. Since depletion of [Ca2+]o led to only partial attenuation of the enhanced response to ET-1 in the treatment groups, it is likely that PKC inhibition results in an exaggerated intracellular mobilization of Ca2+ to ET-1. It is concluded that PKC modulates agonist(s)-evoked intracellular Ca2+ mobilization and that the nature of regulation is governed by the agonist.
Xu
Y
Y
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Sandirasegarane
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L
Gopalakrishnan
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V
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D016257:Fura-2; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D019311:Staurosporine
D000470:Alkaloids; D016232:Endothelins; D010880:Piperidines; D000804:Angiotensin II; D001127:Arginine Vasopressin; C069701:NPC 15437; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium; D016257:Fura-2