A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells
T. Higaki et al., A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells, MICROVASC R, 58(2), 1999, pp. 144-155
The purpose of this study was to elucidate the mechanism by which bradykini
n (BK) enhances prostacyclin (PGI(2)) production in human umbilical vein en
dothelial cells (HUVEC). BK-induced enhancement of PGI(2) synthesis was obs
erved in a dose- and time-dependent manner, and it also increased [Ca2+](i)
followed by enhancement of cytosolic phospholipase A(2) (cPLA(2)) activity
. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in
[Ca2+](i) and inhibited the BK-induced PGI(2) synthesis. Phorbol 12-myrist
ate 13-acetate increased cPLA(2) activity and PGI(2) synthesis but failed t
o alter [Ca2+](i). BK increased cPLA(2) mRNA eightfold by 15 min, and this
increase was inhibited by pretreatment with the PKC inhibitors. In response
to cycloheximide pretreatment, cPLA(2) mRNA was superinduced. These result
s suggest that BK stimulates PGI(2) synthesis in HUVEC by activation of cPL
A(2) by dual mechanisms: an elevation of [Ca2+](i) and a PKC-dependent path
way. Moreover, changes in calcium kinetics and expression of cPLA(2) mRNA m
ay underlie the BK-induced PGI(2) enhancement in these cells. (C) 1999 Acad
emic Press.