Inhibition of histamine secretion from mast cells by lipoxygenase- and cyclooxygenase inhibitors.

We have investigated the effect of inhibitors of lipoxygenase (LOX), cyclooxygenase (COX) and dual inhibitors of both enzymes on the degranulation of peritoneal rat mast cells (pRMC) activated by different mechanisms. COX inhibitors weakly affected histamine secretion induced by A23187 and did not influence the histamine secretion induced by protamine in an isotonic medium but blocked protamine-induced release in a hypertonic medium. LOX- and dual-inhibitors inhibited secretion induced by A23187 and protamine under all conditions. As A23187 activates pRMC in an isotonic medium by Ca influx, and protamine acts in a hypertonic medium by mobilization of intracellular Ca and in an isotonic medium by both processes (this paper), LOX but not COX inhibitors, may block Ca influx, and both prevent Ca mobilization.