EFFECT OF OKADAIC ACID ON HUMAN BASOPHIL SECRETION

We examined the effects of a phosphatase inhibitor, okadaic acid, on m ediator secretion from human basophils. These cells are known to respo nd to a number of stimuli that appear to utilize distinct biochemical pathways converging on mediator release. Okadaic acid was found to inh ibit IgE-mediated release (histamine release inhibited 80 +/- 12% and leukotriene release inhibited 100% following a 10-min preincubation wi th okadaic acid and stimulation with an optimal concentration of anti- IgE antibody) at a concentration of 1 uM. The concentration-response c urve to okadaic acid was steep, with 0.1 muM yielding only 20 +/- 10% inhibition of either mediator. Secretion following stimulation with th e univalent stimulus, fMet-Leu-Phe peptide, was not inhibited by okada ic acid. Unlike cAMP-active agents that inhibit cytosolic Ca2+ elevati ons following IgE-mediated stimulation, the increased state of cellula r protein phosphorylation, which presumably results from treatment wit h 1 muM okadaic acid, had no effect on the elevations in free cytosoli c Ca2+ that follow stimulation with anti-IgE antibody of fMet peptide.