Stimulation of histamine release and arachidonic acid metabolism in rat peritoneal mast cells by thapsigargin, a non-TPA-type tumor promoter

Kazuo Ohuchi, Chikako Takahashi, Noriyasu Hirasawa, Masako Watanabe, Hirota Fujiki, Susumu Tsurufuji

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Thapsigargin, a non-TPA-type tumor promoter, releases histamine and stimulates arachidonic acid metabolism in rat peritoneal mast cells. In order to clarify the relationship between the histamine-releasing activity and the arachidonic acid metabolism-stimulating activity of thapsigargin in mast cells, the effects of cyclooxygenase inhibitors, indomethacin and ibuprofen, a lipoxygenase inhibitor, AA861, and dual inhibitors for cyclooxygenase and lipoxygenase, nordihydroguaiaretic acid and BW755C, on histamine release and arachidonic acid metabolism were examined. High-performance liquid chromatography analysis revealed that the peritoneal mast cells preferentially produce prostaglandin D2 by thapsigargin treatment. These inhibitors suppressed thapsigargin-induced prostaglandin D2 production in a dose-dependent manner, but failed to inhibit histamine release, suggesting that the mechanisms for stimulation of histamine release by thapsigargin is not dependent on increased arachidonic acid metabolism. Time-course experiments of histamine release and the release of radioactivity from [3H]arachidonic acid-labeled mast cells also provide evidence for a difference in mechanism.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1003
Issue number1
DOIs
Publication statusPublished - 1989 May 15

Keywords

  • (Rat peritoneal mast cell)
  • Arachidonic acid metabolism
  • Histamine release
  • Prostaglandin D
  • Thapsigargin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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