Modulation of histamine secretion from Concanavalin A-activated rat mast cells by phosphatidyl serine, calcium, cAMP, pH and metabolic inhibitors.

Concanavalin A (con A) on its own released about half the histamine of peritoneal mast cells from three strains of rats. Phosphatidyl serine (PS) potentiated the release to about 80%. The secretory process had a calcium-independent component of 15--20% at pH 7.5, which increased to a maximum of 40% at pH 6.5 and nearly disappeared at pH 8.0. It was not affected by PS. In the presence of calcium and PS release was maximal and maintained at pH 7 to 8. Inhibitors of oxidative and glycolytic metabolism and dibutyryl cAMP (db cAMP) blocked secretion. The metabolic inhibitors were active whether or not PS was present, whereas db cAMP blocked much less effectively in the presence of PS. Dibutyryl cAMP reduced calcium uptake and this action was also impaired by PS. The active state induced by con A was relatively stable compared with that induced by antigen. Mast cells with a low response to anti-IgE also reponded poorly to con A on its own, but con A plus PS was a highly effective stimulus.