Analysis of the stimulative effect of thapsigargin, a non‐TPA‐type tumour promoter, on arachidonic acid metabolism in rat peritoneal macrophages

Kazuo Ohuchi, Tadaki Sugawara, Masako Watanabe, Noriyasu Hirasawa, Susumu Tsurufuji, Hirota Fujiki, S. Brøgger Christensen, Takashi Sugimura

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49 Citations (Scopus)

Abstract

At concentrations above 10 ng ml−1, the tumour promoter thapsigargin stimulates the release of radioactivity from [3H]‐arachidonic acid‐labelled macrophages harvested from rat peritoneal cavity. The release of radioactivity from prelabelled macrophages was augmented more than additively when the cells were incubated in the medium containing both thapsigargin (10 ng ml−1) and other tumour promoters (10 ng ml−1), such as 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), teleocidin and aplysiatoxin. Thapsigargin required extracellular Ca2+ for the stimulation of arachidonic acid release, while TPA did not. Cytoplasmic free calcium level was increased by thapsigargin treatment but not by TPA treatment. An inhibitor of protein kinases, H‐7 inhibited the effect of TPA dose‐dependently, whereas H‐7 did not inhibit that of thapsigargin. These results suggest that thapsigargin stimulates arachidonic acid release by a mechanism different from that of TPA, viz by acting as a selective Ca2+ mobilizer, but not by activating protein kinase C as TPA does. 1988 British Pharmacological Society

Original languageEnglish
Pages (from-to)917-923
Number of pages7
JournalBritish Journal of Pharmacology
Volume94
Issue number3
DOIs
Publication statusPublished - 1988 Jul

ASJC Scopus subject areas

  • Pharmacology

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