Effect of okadaic acid on human basophil secretion.
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 microM. The concentration-response curve to okadaic acid was steep, with 0.1 microM 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 microM okadaic acid, had no effect on the elevations in free cytosolic Ca2+ that follow stimulation with anti-IgE antibody of fMet peptide.
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
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D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E; D015289:Leukotrienes / Q000378:metabolism; D009239:N-Formylmethionine; D019319:Okadaic Acid; D015398:Signal Transduction
D004988:Ethers, Cyclic; D015289:Leukotrienes; D019319:Okadaic Acid; D007073:Immunoglobulin E; D009239:N-Formylmethionine; D006632:Histamine; D002118:Calcium