Inhibitory effects of tributyltin on dopamine biosynthesis in rat PC12 cells

Abstract

The inhibitory effects of tributyltin chloride (TBTC) on dopamine biosynthesis in PC12 cells were investigated. Twenty-four hour exposure to TBTC at 0.5 μM showed 32.9% inhibition of dopamine content: the IC 50 value of TBTC was 0.72 μM. Dopamine content decreased at 6 h and reached a minimal level at 24 h after exposure to TBTC at 0.5 μM. The decreased dopamine level was maintained for up to 48 h. Under these conditions, tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with TBTC and the activity was maintained at a reduced level for up to 48 h (20–35% inhibition at 0.5 μM of TBTC). TH mRNA level also started to decrease at about 6 h and reached a minimal level at 24 h after exposure of PC12 cells to TBTC. In addition, treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) at 20–50 μM increased the intracellular dopamine content in PC12 cells and the increase of dopamine level by L-DOPA was significantly inhibited after exposure to TBTC at 0.5–2.0 μM for 24 h. These results indicate that TBTC decreases dopamine content by the inhibition of TH activity and TH mRNA level in PC12 cells. It is, therefore, proposed that TBTC may exacerbate the Parkinson's symptoms because of the inhibition of dopamine biosynthesis and dopamine increase induced by L-DOPA.