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Tetrahydropapaveroline의 PC12 세포내 Dopamine 생합성 저해작용
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  • Tetrahydropapaveroline의 PC12 세포내 Dopamine 생합성 저해작용
  • Inhibitory Effects of Tetrahydropapaveroline on Dopamine Biosynthesis in PC12 Cells
저자명
이재준,김유미,김미나,이명구,Lee. Jae-Joon,Kim. Yu-Mi,Kim. Mi-Na,Lee. Myung-Koo
간행물명
약학회지
권/호정보
2005년|49권 2호|pp.156-161 (6 pages)
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Tetrahydropapaveroline (THP) at 5-15 ${mu}$M has been found to induce L-DOPA-induced oxidative apoptosis in PC12 cells. In this study, the inhibitory effects of THP on dopamine bios ynthesis in PC12 cells and tyrosine hydroxylase (TH) activity in bovine adrenal were investigated. Treatment of PC12 cells with THP at 2.5-10 ${mu}$M significantly decreased the intracellular dopamine content in a concentration-dependent manner (18.3% inhibition at 10 ${mu}$M THP). In these conditions, TH activity was markedly inhibited by the treatment with THP at 2.5-10 ${mu}$M in PC12 cells (23.4% inhibition at 10 $mu$ M THP). In addition, THP had an inhibitory effect on bovine adrenal TH activity IC50 value, 153.9${mu}$M). THP exhibited uncompetitive inhibition on bovine adrenal TH activity with a substrate L-tyrosine with the KI value of 0.30 mM. Treatment with L-DOPA at 20~50 ${mu}$M increased the intracellular dopamine content in PC12 cells, and the increase in dopamine content by L-DOPA was inhibited in part when THP at non-cytotoxic (5-10 ${mu}$M) or cytotoxic (15${mu}$M) concentrations was associated with L-DOPA (20 and 50 ${mu}$M) for 24 h incubation. These results suggest that THP at 5-10${mu}$M decreases the basal dopamine content and reduces the increased dopamine content induced by L-DOPA in part by the inhibition of TH activity, and that THP at 15${mu}$M also decreases dopamine content by oxidative stress in PC12 cells.