Tetrahydropapaveroline의 PC12 세포내 Dopamine 생합성 저해작용

• 영문명: Inhibitory Effects of Tetrahydropapaveroline on Dopamine Biosynthesis in PC12 Cells
• 발행기관: 대한약학회
• 저자명: 이재준(Jae Joon Lee) 김유미(Yu Mi Kim) 김미나(Mi Na Kim) 이명구(Myung Koo Lee)
• 간행물 정보: 『약학회지』제49권 제2호 (2005년), 156~161쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2005.04.30

영문 초록

Tetrahydropapaveroline (THP) at 5-15 μM has been found to induce L-DOPA-induced oxidative apoptosis in PC12 cells. In this study, the inhibitory effects of THP on dopamine biosynthesis in PC12 cells and tyrosine hydroxylase (TH) activity in bovine adrenal were investigated. Treatment of PC12 cells with THP at 2.5-10 μM significantly decreased the intracellular dopamine content in a concentration-dependent manner (18.3% inhibition at 10 μM THP). In these conditions, TH activity was markedly inhibited by the treatment with THP at 2.5-10 μM in PC12 cells (23.4% inhibition at 10 μM THP). In addition, THP had an inhibitory effect on bovine adrenal TH activity IC50 value, 153.9μM). 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 μM 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 μM) or cytotoxic (15μM) concentrations was associated with L-DOPA (20 and 50 μM) for 24 h incubation. These results suggest that THP at 5-10μM 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 15μM also decreases dopamine content by oxidative stress in PC12 cells.

키워드

tetrahydropapaveroline dopamine tyrosine hydroxylase PC 12 cells bovine adrenal