THE EFFECT OF ANISODAMINE ON ENDOTOXIN-STIMULATED PROSTAGLANDIN SYNTHESIS BY MACROPHAGES AND ENDOTHELIAL CELLS

Anisodamine, an alkaloid isolated from the Chinese herb Anisodas tanguticus and later synthesized, has been used as an antishock drug in China for two decades. This study attempted to determine if anisodamine affects arachidonic acid metabolism in cultured cells. Results indicate that endotoxin-stimulated synthesis of cyclooxygenase products including prostacyclin (measured as 6-keto-PGF_1α), thromboxane A₂ (measured as TXB₂) and prostaglandin F_2α (PGF_2α) in mice peritoneal macrophages was dose-dependently inhibited by anisodamine at dosages of 0.1～0.5 mg/ml, Preincubation of macrophages with anisodamine (0.5 mg/ml) for 2 h significantly decreased subsequent endotoxin-stimulated 6-keto-PGF_1α and TXB₂ production, In ³H-arachidonic acid prelabelled bovine aorta endothelial cells, both the release of ³H-labelled compounds and-production of 6-keto-PGF_1α were inhibited by anisodamine. It is suggested that anisodamine directly inhibited endotoxin-stimulated prostaglandin synthesis by cells in culture and its site of action might be at the cyclooxygenase reaction or, more likely, at the process of deesterification of cellular lipids.