Inhibitory effect of tetrandrine on dopamine biosynthesis and tyrosine hydroxylase in PC12 cells.

The effect of tetrandrine, a bis-benzylisoquinoline alkaloid, on dopamine biosynthesis in PC12 cells was investigated. Tetrandrine at a concentration of 3.0 microM decreased dopamine content by 59.4% (IC50 = 2.4 microM) and intracellular tyrosine hydroxylase (TH) activity was inhibited by the treatment of tetrandrine (49.8% inhibition at 3.0 microM) compared with control. We next examined the effects of tetrandrine on the kinetics of PC12 TH. The PC12 TH was obtained from PC12 cells with minor purification. Tetrandrine inhibited the PC12 TH activity by 40.6% at a concentration of 45 microM and exhibited noncompetitive inhibition on the enzyme using L-tyrosine as a substrate (Ki = 60.8 microM). These results suggest that the inhibition of TH activity by tetrandrine may partially contribute to the decrease in dopamine biosynthesis in PC12 cells.