INHIBITORY EFFECT OF FANGCHINOLINE ON DOPAMINE BIOSYNTHESIS IN PC12 CELLS

We have investigated the effects of fangchinoline, a bis-benzylisoquinoline alkaloid, on dopamine biosynthesis in PC12 cells. Fangchinoline at a concentration of 6.0 mu M reduced the dopamine content by 60.1% as compared with the control. The IC50 value of fangchinoline was 3.8 mu M. In this condition, tyrosine hydroxylase (TH) activity was inhibited by the fangchinoline treatment (48.5% inhibition at 6.0 mu M) We next examined the effects of fangchinoline on the kinetics of PC12 TK. The PC12 TH was obtained from PC12 cells with minor purification. Fangchinoline inhibited the PC12 TH activity by 43.9% at a concentration of 60 mu M and exhibited non-competitive inhibition on the enzyme using L-tyrosine as a substrate. The K-i value of fangchinoline was 0.10 mM. These results suggest that the inhibition of TH activity by fangchinoline may partially contribute to the decrease in dopamine biosynthesis in PC12 cells. Med Sci Res 26:475-476 (C) 1998 Lippincott-Raven Publishers.