Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [14C]arachidonic acid and histamine from rat peritoneal mast cells.
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 [14C]arachidonic acid and histamine release. A minor amount of the released [14C]arachidonic acid was converted to [14C]prostaglandin D2. A potentiated effect was found between thapsigargin and 12-O-tetradecanoylphorbol 13-acetate, as well as between A23187 and the phorbol ester with respect to release of [14C]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. [14C]arachidonic acid was released mainly from phosphatidylcholine. It is suggested that this release may be due to an action of phospholipase A2, and that protein kinase C is involved in activation of phospholipase A2.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002250:Carbon Radioisotopes; D004357:Drug Synergism; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019284:Thapsigargin
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D010936:Plant Extracts; D011457:Prostaglandins D; D016718:Arachidonic Acid; D000001:Calcimycin; D019284:Thapsigargin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; D002118:Calcium