Endothelin-1-evoked arachidonic acid release: a Ca2+-dependent pathway

Amino acid release studies revealed a significantly high production of arachidonic acid (AA) in human pericardial smooth muscle cells (HPSMC) exposed to endothelin-1 (ET-1). Similar results were observed in cell cultures containing the calcium (Ca2+) ionophore A-23187 at 2 mumolars and extracellular Ca2+. Removal of the Ca2+ source markedly reduced ET-1-evoked AA release. Exposure of cells to inhibitors of protein kinase C reduced ET-1-evoked AA release by 70%, whereas inhibitors of phospholipase A2 potentiated the effects of ET-1. These results suggest that ET-1-evoked AA release in HPSMC could be promoted by phospholipase A2.