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比较多巴胺和左旋多巴对大鼠肝脏芳基硫酸转移酶和雌激素硫酸转移酶的诱导作用(英文)
引用本文:邵雪岩,;李健,;王思媛,;陈广平,;许娇娇,;冀希炜,;李良,;卢炜,;周田彦.比较多巴胺和左旋多巴对大鼠肝脏芳基硫酸转移酶和雌激素硫酸转移酶的诱导作用(英文)[J].中国药学,2014,23(7):471-479.
作者姓名:邵雪岩  ;李健  ;王思媛  ;陈广平  ;许娇娇  ;冀希炜  ;李良  ;卢炜  ;周田彦
作者单位:[1]北京大学医学部药学院药剂学系,北京100191; [2]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191; [3]奥克拉荷马州立大学动物医学中心生理学系,美国OK74078
基金项目:National Natural Science Foundation of China(Grant No.81072699)
摘    要:硫酸转移酶是主要的II相药物代谢酶之一。芳基硫酸转移酶包括rSULT1A1和rSULT1E1,能够催化酚类化合物发生硫酸化。多巴胺是中枢神经系统重要的神经递质,并且能调控各种外周功能。本研究旨在探究多巴胺和左旋多巴对大鼠肝脏硫酸转移酶(rSULT1A1,rSULT1E1)的作用。分别给予雄性大鼠、雌性大鼠不同浓度多巴胺(0,2,10,100 mg/kg/d)及左旋多巴(0,5,25,125 mg/kg/d)。采用real-time PCR以及western blot方法测定rSULT1A1和rSULT1E1的mRNA和蛋白表达;采用PNPS以及放射性的方法测定rSULT1A1和rSULT1E1活性。结果表明:多巴胺增加两种性别大鼠肝脏中rSULT1A1的表达和活性,而对rSULT1E1无显著作用;左旋多巴仅对雄性大鼠肝脏的rSULT1E1有诱导作用,但对两种大鼠肝脏中rSULT1A1以及雌性大鼠的rSULT1E1未产生显著作用。研究结果说明多巴胺在外周和中枢神经系统对rSULTA1和rSULTE1的诱导作用是不同的。

关 键 词:多巴胺  左旋多巴  多巴胺受体  硫酸转移酶  诱导

Comparison of dopamine with levodopa in the induction of aryl sulfotransferases and estrogen sulfotransferase in rat liver
Xueyan Shao,Jian Li,Siyuan Wang,Guangping Chen,Jiaojiao Xu,Xiwei Ji,Liang Li,Wei Lu,Tianyan Zhou.Comparison of dopamine with levodopa in the induction of aryl sulfotransferases and estrogen sulfotransferase in rat liver[J].Journal of Chinese Pharmaceutical Sciences,2014,23(7):471-479.
Authors:Xueyan Shao  Jian Li  Siyuan Wang  Guangping Chen  Jiaojiao Xu  Xiwei Ji  Liang Li  Wei Lu  Tianyan Zhou
Institution:Xueyan Shao, Jian Li, Siyuan Wang, Guangping Chen, Jiaojiao Xu, Xiwei Ji, Liang Li, Wei Lu, Tianyan Zhou( 1. Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Health Science Center, Beij'ing 100191, China 2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China 3. Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater 0K74078, USA)
Abstract:Sulfotransferases(SULTs) are one of the most important phase II drug-metabolizing enzymes. Among them, aryl sulfotransferases(SULT1A1) and estrogen sulfotransferase(EST, SULT1E1) belong to the rSULT1 family that catalyzes sulfation of phenolic compounds. Dopamine(DA) acts as a vital neurotransmitter in central nervous system(CNS) and regulates a variety of activities in periphery. In our study, we aim to detect the effects of exogenous DA and levodopa(L-DOPA) on rSULTs(rSULT1A1 and rSULT1E1) in rat liver. In order to achieve this target, varying doses of DA(0, 2, 10 and 100 mg/kg/d) and L-DOPA(0, 5, 25 and 125 mg/kg/d) were provided to male and female rats, respectively. Real-time PCR assay and western blot were used in the determination of the mRNA and protein expression of rSULTs. PNPS assay and radioactivity assay were applied to the detection of enzyme activity of rSULT1A1 and rSULT1E1, respectively. Our results showed that DA induced the expression and activity of rSULT1A1 in the liver of male and female rats and DA had little effect on rSULT1E1. However, L-DOPA caused no evident change of rSULT1A1 in both sex and had no significant effect on rSULT1E1 in female rat liver, but increased rSULT1E1 expression and activity only in male rat liver when administered at high dose. Our results suggest that DA plays different roles in the regulation of rSULT1A1 and rSULT1E1 when it is in periphery or in the CNS.
Keywords:Dopamine  Levodopa  Dopamine receptors  Sulfotransferase  Induction
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