ANGIOTENSIN-II STIMULATES PHOSPHORYLATION OF HIGH-MOLECULAR-MASS CYTOSOLIC PHOSPHOLIPASE A(2) IN VASCULAR SMOOTH-MUSCLE CELLS

Phospholipase A(2) (PLA(2)) may be one of the major components involved in cell signalling and proliferation, as suggested by recent studies. In this paper we show that the potent vasoconstrictor and hypertrophic agent angiotensin II (AngII) activates cytosolic PLA(2) (cPLA(2)) in vascular smooth-muscle cells. AngII induced a rapid time-dependent release of[H-3]arachidonic acid from prelabelled cells that was inhibited by mepacrine, a PLA(2) inhibitor. AngII treatment of intact cells also activated a cPLA(2), as measured in cell-free extracts by the release of radiolablled arachidonic acid from exogenously added 1-stearoyl-2-[1-C-14]arachidonoyl phosphatidylcholine. This AngII-stimulated cPLA(2) activity was also significantly inhibited by mepacrine. AngII induced a rapid and time-dependent increase in cPLA(2) phosphorylation. Protein kinase C (PKC) depletion inhibited both AngII-induced [H-3]arachidonic acid release and cPLA(2) phosphorylation. Together, these results suggest strongly that (1) AngII phosphorylates and activates cPLA(2) in a PKC-dependent manner, and that (2) cPLA(2), mediates the AngII-induced [H-3]arachidonic acid release in vascular smooth-muscle cells.