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Analysis of the stimulative effect of thapsigargin, a non‐TPA‐type tumour promoter, on arachidonic acid metabolism in rat peritoneal macrophages
Author(s) -
Ohuchi Kazuo,
Sugawara Tadaki,
Watanabe Masako,
Hirasawa Noriyasu,
Tsurufuji Susumu,
Fujiki Hirota,
Christensen S. Brøgger,
Sugimura Takashi
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11604.x
Subject(s) - thapsigargin , arachidonic acid , extracellular , stimulation , endocrinology , calcium , tetradecanoylphorbol acetate , medicine , protein kinase c , chemistry , biology , kinase , biochemistry , microbiology and biotechnology , enzyme
1 At concentrations above 10 ng ml −1 , the tumour promoter thapsigargin stimulates the release of radioactivity from [ 3 H]‐arachidonic acid‐labelled macrophages harvested from rat peritoneal cavity. 2 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. 3 Thapsigargin required extracellular Ca 2+ for the stimulation of arachidonic acid release, while TPA did not. 4 Cytoplasmic free calcium level was increased by thapsigargin treatment but not by TPA treatment. 5 An inhibitor of protein kinases, H‐7 inhibited the effect of TPA dose‐dependently, whereas H‐7 did not inhibit that of thapsigargin. 6 These results suggest that thapsigargin stimulates arachidonic acid release by a mechanism different from that of TPA, viz by acting as a selective Ca 2+ mobilizer, but not by activating protein kinase C as TPA does.