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Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

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Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C]arachidonic acid was converted to [C]prostaglandin D. A potentiated effect was found between thapsigargin and 12--tetradecanoylphorbol 13-acetate, as well as between A23187 and the phorbol ester with respect to release of [C]arachidonic acid and histamine. It is suggested that the synergistic effect is due to activation of protein kinase C by 12-O-tetradecanoylphorbol 13-acetate and to increased intracellular calcium concentration mediated by A23187 as well as thapsigargin. [C]arachidonic acid was released mainly from phosphatidylcholine. It is suggested that this release may be due to an action of phospholipase A, and that protein kinase C is involved in activation of phospholipase A.
OriginalsprogEngelsk
TidsskriftBiochemical Pharmacology
Vol/bind36
Udgave nummer5
Sider (fra-til)621-626
Antal sider6
ISSN0006-2952
StatusUdgivet - 1 mar. 1987

ID: 45561308