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

doi:10.5246/jcps.2014.07.062

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (7): 471-479.DOI: 10.5246/jcps.2014.07.062

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

邵雪岩¹, 李健¹, 王思媛¹, 陈广平³, 许娇娇¹, 冀希炜¹, 李良¹, 卢炜^1,2, 周田彦^1,2*

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

收稿日期:2014-04-04 修回日期:2014-05-13 出版日期:2014-07-18 发布日期:2014-05-25
通讯作者: Tel.: 86-10-82805937, Fax: 86-10-82801717
基金资助:
National Natural Science Foundation of China (Grant No. 81072699).

Comparison of dopamine with levodopa in the induction of aryl sulfotransferases and estrogen sulfotransferase in rat liver

Xueyan Shao¹, Jian Li¹, Siyuan Wang¹, Guangping Chen³, Jiaojiao Xu¹, Xiwei Ji¹, Liang Li¹, Wei Lu^1,2, Tianyan Zhou^1,2*

1. Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Health Science Center, Beijing 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 OK74078, USA

Received:2014-04-04 Revised:2014-05-13 Online:2014-07-18 Published:2014-05-25
Contact: Tel.: 86-10-82805937, Fax: 86-10-82801717
Supported by:
National Natural Science Foundation of China (Grant No. 81072699).

摘要/Abstract

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

Abstract:

Sulfotransferases (SULTs) are one of the most important phase IIdrug-metabolizing enzymes. Among them, aryl sulfotransferases (SULT1A1) and estrogen sulfotransferase (EST, SULT1E1) belong to the rSULT1family that catalyzes sulfation of phenoliccompounds. 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 inducedthe 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.

Key words: Dopamine, Levodopa, Dopamine receptors, Sulfotransferase, Induction

中图分类号:

R962

Supporting:

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[J]. 中国药学(英文版), 2014, 23(7): 471-479.

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.

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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

Comparison of dopamine with levodopa in the induction of aryl sulfotransferases and estrogen sulfotransferase in rat liver

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