Inhibitory effects of tributyltin on dopamine biosynthesis in rat PC12 cells.
The inhibitory effects of tributyltin chloride (TBTC) on dopamine biosynthesis in PC12 cells were investigated. Twenty-four hour exposure to TBTC at 0.5 microM showed 32.9% inhibition of dopamine content: the IC(50) value of TBTC was 0.72 microM. Dopamine content decreased at 6 h and reached a minimal level at 24 h after exposure to TBTC at 0.5 microM. 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 microM 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 microM 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 microM 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.
Kim
Yu Mi
YM
College of Pharmacy, Chungbuk National University, San 48, Kaeshin-Dong, Heungduk-Ku, Cheongju 361-763, South Korea.
Lee
Jae Joon
JJ
Yin
Shou Yu
SY
Kim
Youngsoo
Y
Lee
Jong Kil
JK
Yoon
Yeo Pyo
YP
Kang
Min Hee
MH
Lee
Myung Koo
MK
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016716:PC12 Cells; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D018492:Dopamine Antagonists; D012333:RNA, Messenger; D014220:Trialkyltin Compounds; C011559:tributyltin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine