Inhibition by amiloride and by Na+-depletion of A23187-stimulated arachidonic acid and histamine release from rat mast cells.

Rat peritoneal mast cells, labelled with [14C]arachidonic acid, released histamine and [14C]arachidonic acid upon the addition of A23187. The release induced by low concentrations of A23187 was suppressed by removal of extracellular Na+ and by addition of the Na+/H+ exchange inhibitor, amiloride. Addition of protein kinase C inhibitors resulted in only a modest decrease of [14C]arachidonic acid and histamine release. [14C]Arachidonic acid was hydrolyzed from both phosphatidylcholine and triacylglycerol. Amiloride inhibited only the hydrolysis from phosphatidylcholine. It is suggested that an Na+/H+ exchange is stimulated secondary to an A23187-induced increase in intracellular calcium concentration. Increased Na+/H+ exchange seems to facilitate the activation by intracellular calcium ions of phospholipase A2 as well as of histamine secretion.