Characteristics of the effect of phorbol ester on rat mast cells: interaction with anti-IgE

The phorbol ester 12-0-tetradecanoyl-13-acetate (TPA) induced a dose-dependent release of histamine from rat peritoneal mast cells at concentrations from 3 to 100 ng/ml. The release is biphasic: an early phase being complete in 15 min and being followed by a second phase extending for more than 50 min. Concentrations of TPA greater than 100 ng/ml produced decreasing releases of histamine. Synergistic interaction in the induction of histamine secretion was observed between TPA and A23187 and between TPA and anti-IgE. Such synergism with anti-IgE was only manifest at low concentrations of TPA and with incubations of the cells with TPA for 5 mins or less. At higher concentrations of TPA and longer incubations, TPA inhibited the response of rat peritoneal mast cells to anti-IgE stimulation. Synergism between A23187 and TPA was observed only at low levels of histamine release induced by calcium plus A23187: at higher levels of release TPA was inhibitory.