Maitotoxin, a novel activator of mediator release from human basophils, induces large increases in cytosolic calcium resulting in histamine, but not leukotriene C4, release

M. Columbo, M. Taglialatela, J. A. Warner, D. W. MacGlashan, T. Yasumoto, L. Annunziato, G. Marone

Research output: Contribution to journalArticle

Abstract

Maitotoxin (MTX) is a potent marine toxin which stimulates several Ca++- dependent processes presumably through an increase in Ca++ permeability. We have examined the effect of MTX on the release of chemical mediators from human basophils and its mechanism of action. MTX (1-20 ng/ml) induced histamine release (37-100%) from both mixed leukocyte preparations and purified basophils. Histamine release activated by MTX was slow (t( 1/2 ) ≃ 15 min), temperature and Ca++ dependent (optimal at 37°C and 1-2.5 mM Ca++). Sr++ ion could substitute for Ca++ in the secretory process. Digital video microscopy analysis of purified (>70%) basophils revealed that MTX (1-20 ng/ml) induced a slow and marked increase of cytosolic Ca++ levels that was temporally coincident with histamine release. MTX (1-20 ng/ml) stimulated the release of sulfidopeptide leukotriene C4 from mixed leukocyte preparations (≃0.5% basophils). However, purified basophils (77 ± 7%) showed no sulfidopeptide leukotriene C4 release even in the presence of large histamine secretion (84 ± 14%). Two organic Ca++-channel entry blockers, verapamil and diltiazem (1-30 μM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 μM) caused only minimal inhibition. These results suggest that MTX represents a novel stimulus useful to study the role of Ca++ in human basophil mediator release.

Original languageEnglish (US)
Pages (from-to)979-986
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number3
StatePublished - Dec 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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