We examined the effects of a phosphatase inhibitor, okadaic acid, on mediator secretion from human basophils. These cells are known to respond to a number of stimuli that appear to utilize distinct biochemical pathways converging on mediator release. Okadaic acid was found to inhibit IgE-mediated release (histamine release inhibited 80 ± 12% and leukotriene release inhibited 100% following a 10-min preincubation with okadaic acid and stimulation with an optimal concentration of anti-IgE antibody) at a concentration of 1 μM. The concentration-response curve to okadaic acid was steep, with 0.1 μM yielding only 20 ± 10% inhibition of either mediator. Secretion following stimulation with the univalent stimulus, fMet-Leu-Phe peptide, was not inhibited by okadaic acid. Unlike cAMP-active agents that inhibit cytosolic Ca2+ elevations following IgE-mediated stimulation, the increased state of cellular protein phosphorylation, which presumably results from treatment with 1 μM okadaic acid, had no effect on the elevations in free cytosolic Ca2+ that follow stimulation with anti-IgE antibody of fMet peptide.
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