AJP - Endocrinology and Metabolism, Vol 263, Issue 4 E800-E806, Copyright © 1992 by American Physiological Society
Regulation of prostacyclin production by [Ca2+]i and protein kinase C in aortic smooth muscle cells
A. C. Erbrich, D. J. Church, M. B. Vallotton and U. Lang
Department of Medicine, University Hospital, Geneva, Switzerland.
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.
