Effects of tetrandrine on production of leukotriene B4 and thromboxane B2 in rabbit blood

The effects of tetrandrine (Tet) on the production of 2 major metabolites of arachidonic acid (AA), the leukotriene B4 (LTB4) and the thromboxane B2 (TXB2) in rabbit whole blood were investigated by reversed phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA), respectively. After incubation with different doses of Tet for 15 min in vitro, the production of LTB4 and TXB2 by rabbit whole blood stimulated with calcimycin (20 mumol.L-1) was inhibited in a dose-dependent manner, with IC50 value of 17.8 +/- 8.6 and 17.7 +/- 9.2 mumol.L-1, respectively. In the presence of exogenous AA, the inhibitory effects of Tet were markedly lessened. The effects of Tet were much like those of calmodulin (CaM) antagonist fluphenazine (Flu). Dexamethasone (Dex) also inhibited the production of LTB4 and TXB2 when incubated with rabbit whole blood for 60 min. Tet iv 10 mg.kg-1 also inhibited the production of LTB4 and TXB2 in rabbit whole blood stimulated with calcimycin. These results suggest that Tet may be an antagonist of CaM, thus suppressing the release of AA which was catalyzed by CaM dependent phospholipase A2 (PLA2) from the membrane phospholipids of blood cells.