Endothelin action: Inhibition by a protein kinase C inhibitor and involvement of phosphoinositols

Results indicate that phosphatidylinositol turnover and protein kinase C activation are involved in endothelin-induced vasoconstriction.

Abstract

Endothelin tightly bound to rabbit aortic strips and caused a prolonged vasoconstriction both in the presence and absence of extracellular Ca2+, although only partial constriction (20-30%) developed in the latter case, indicating that its action may not be limited to the opening of a calcium channel. The endothelin-induced constriction was reversed by the protein kinase C inhibitor, 1-(5-isoquinolynylsulfonyl)-2-methylpiperazine (H-7). In contrast to the observation of Hirata et al (1), endothelin caused a robust phosphatidylinositol breakdown producing inositol mono-, bis-and trisphosphates in cultured rat vascular smooth muscle cells. It showed no effect on cyclic nucleotide levels in the same cultured cells. These results indicate that phosphatidylinositol turnover and protein kinase C activation are involved in endothelin-induced vasoconstriction.