Gk. Oriji, Endothelin-induced prostacyclin production in rat aortic endothelial cellsis mediated by protein kinase C, PROS LEUK E, 60(4), 1999, pp. 263-268
Citations number
39
Categorie Soggetti
Cell & Developmental Biology
Journal title
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
Endothelin (ET) is a vasoconstrictor peptide released from endothelial cell
s that is known to cause prostaglandin (PG) release. The mechanism remains
unclear. To determine whether the protein kinase C (PKC) signaling pathway
is stimulated by endothelin, we pretreated rat aortic endothelial cells wit
h either PKC activator or inhibitors and measured the release of prostacycl
in (PGI(2)) by radioimmunoassay. ET (10(-9) M) produced a 10-fold increase
in PGI(2) release. Pretreatment with 10(-9) M of three different PKC inhibi
tors: 1-(5-isoquinolinesulfonyl) piperazine (CL), staurosporine, and 1-(5-i
soquinolinesulfonyl-methyl) piperazine (H7) blocked ET induced PGI(2) relea
se. ET induced prostacyclin release was also blocked by pretreatment with i
nhibitors of either phospholipase A(2) (7,7,dimethyleicosadienoic acid or t
rifluoromethyl ketone analogue) (10-9 M) or cyclooxygenase (indomethacin) (
10(-9)M). We conclude that ET activates PKC which activates phospholipase A
(2) which liberates arachidonic acid which increases PGI, production and re
lease.