Endothelin‐1 Increases Arachidonic Acid Release in C6 Glioma Cells Through a Potassium‐Modulated Influx of Calcium

: Endothelin‐1 (Et‐1) but not a range of other receptor agonists stimulated the release of arachidonic acid (AA) in C6 glioma. Et‐1 activation was concentration dependent and was inhibited by chelation of extracellular calcium. The calcium ionophores A23187 and ionomycin could also stimulate release of AA. Et‐1 caused an early increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) followed by a sustained but lower plateau level. The sensitivity of the response to quinacrine, its dependence on Ca 2+ , and the demonstration of an increase in phospholipase A 2 (PLA 2 ) activity that was insensitive to dithiothreitol suggested that the release of AA was due to activation of cytosolic PLA 2 in the cells. Staurosporine, a protein kinase C (PKC) inhibitor, had no effect on Et‐1‐induced AA release but abolished that by phorbol 12‐myristate 13‐acetate, demonstrating that the Et‐1 response was PKC independent. Raised levels of extracellular KCI inhibited both AA release and the increase in [Ca 2+ ] i triggered by Et‐1, whereas valinomycin, which causes K + efflux, not only caused a rapid rise in [Ca 2+ ] i but also caused AA mobilisation. The results therefore suggest that Et‐1 activation of PLA 2 in this cell type requires calcium influx dependent on K + efflux.