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 metaboli tes of arachidonic acid (AA), the leukotriene B4(LTB4) and the thrombo xane B2(TXB2) in rabbit whole blood were investigated by reversed phas e high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA ), respectively. After incubation with different doses of Tet for 15 m in in vitro , the production of LTB4 and TXB2 by rabbit. whole blood s timulated with calcimycin (20 mumol.L-1) was inhibited in a dose-depen dent 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 effec ts of Tet were markedly lessened. The effects of Tet were much like th ose of calmodulin (CaM) antagonist fluphenazine (Flu). Dexamethasone ( Dex) also inhibited the production of LTB4 and TXB2 when incubated wit h 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 calc imycin. These results suggest that Tet may be an antagonist of CaM, th us suppressing the release of AA which was catalyzed by CaM dependent phospholipase A2(PLA2) from the membrane phospholipids of blood cells.