Inhibitory Effects of Higenamine on Dopamine Content in PC12 Cells

Abstract

The inhibitory effects of (±)-higenamine, a benzyliso-quinoline alkaloid, on dopamine biosynthesis in PC12 cells were investigated. Higenamine decreased the intracellular dopamine content dose-dependently and showed 55.2% inhibition of dopamine content in PC12 cells at a concentration of 20 µM with 24 h incubation. The IC₅₀ value of higenamine was 18.2 µM. Dopamine content was lowered and reached minimal level at 12-24 h after exposure to higenamine. In this condition, tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, was also inhibited by the treatment of higenamine in PC12 cells (21.9% inhibition at 20 µM). Higenamine at 20 µM lowered the intracellular Ca²⁺ concentration by 33.1% inhibition relative to control in PC12 cells. These results suggest that the inhibition of tyrosine hydroxylase activity by higenamine might partially contribute to the decrease in dopamine content in PC12 cells.