EFFECT OF OKADAIC ACID ON IMMUNOLOGICAL AND NONIMMUNOLOGICAL HISTAMINE-RELEASE IN RAT MAST-CELLS

We have studied the effect of the protein phosphatase (PP) inhibitor, okadaic acid (OKA) on histamine release elicited by immunologic and no n-immunologic stimuli in peritoneal and pleural rat mast cells. When c ells were stimulated with antigen (egg albumin), OKA strongly inhibite d histamine release. This finding suggests that PP1 and PP2A substrate s mediate immunoglobulin E-(IgE) dependent secretion in mast cells. In contrast, after non-immunologic activation of mast cells with differe nt drugs, such as the neuropeptide growth hormone releasing factor (GR F) and the cytostatic agents Adriamycin, navelbine and mitoxantrone, t here is no effect of OKA on histamine secretion. These results indicat e that IgE-dependent secretion is mediated by substrates of PP1 and PP 2A, whereas following nonimmunological stimuli, they activate pathways that lead to protein phosphorylation; these proteins are not substrat es of PP1 and PP2A.