Regulation of prostacyclin production by [Ca2+]i and protein kinase C in aortic smooth muscle cells.
The respective roles of protein kinase C (PKC) and of cytosolic free Ca2+ concentration ([Ca2+]i) in prostacyclin synthesis were investigated in aortic smooth muscle cells by using A23187 and phorbol 12-myristate 13-acetate (PMA) to bypass the hormonal receptor. Exposure of the cells to A23187 markedly increased prostacyclin production, which was not affected by the PKC inhibitor staurosporine or by PKC depletion after prolonged incubation (48 h) of cells with PMA. The increase in [Ca2+]i induced by A23187 did not affect membranous or cytosolic PKC activity in control and PMA-stimulated cells. Activation of PKC by PMA, a weak stimulant of prostacyclin production by itself, strongly potentiated A23187-induced prostacyclin production, as well as that induced by the calcium-mobilizing hormone arginine vasopressin (AVP). The potentiating effect persisted for 30 min after the removal of PMA. However, this "memory" effect was not due to sustained levels of membranous PKC activity but probably to the prolonged influence of PKC-induced phosphorylation(s). Taken together, our results suggest that, although an increase in [Ca2+]i is sufficient for inducing prostacyclin production in rat aortic smooth muscle cells, activation of PKC is necessary for AVP-induced prostacyclin production in this same tissue.
Erbrich
A C
AC
Department of Medicine, University Hospital, Geneva, Switzerland.
Church
D J
DJ
Vallotton
M B
MB
Lang
U
U
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004789:Enzyme Activation; D011464:Epoprostenol / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001127:Arginine Vasopressin; D000001:Calcimycin; D011464:Epoprostenol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium