title: Exogenous dopamine induces dehydroepiandrosterone sulfotransferase (rSULT2A1) in rat liver and changes the pharmacokinetic profile of moxifloxacin in rats.
abstract: Dehydroepiandrosterone sulfotransferase (SULT2A1) plays an important role in the detoxification of hydroxyl-containing xenobitotics and in the regulation of the biological activities of hydroxysteroids. Although dopamine (DA) is a vital neurotransmitter, DA also has some special functions in outer peripheral system and takes effect by binding with dopamine receptors including five subtypes (D1-D5). The objective of this study was to investigate the effect of exogenous DA on both the regulation of rSULT2A1 (rat SULT2A1) and the pharmacokinetics of moxifloxacin which is a specific substrate of rSULT2A1. After different doses of DA (0, 2, 10 and 100 mg/kg/d) were administrated to both male and female rats for 7 days, the activity, protein level and mRNA expression of rSULT2A1 increased significantly. Moreover, both Cmax and AUC of moxifloxacin decreased and AUC of moxifloxacin sulfate conjugate metabolite increased significantly when moxifloxacin was administered to rats with DA pretreatment. Additionally, D1 expression in liver and cAMP concentration also increased after the treatment with DA. Overall these results suggest that exogenous DA may induce rSULT2A1 in rat liver and may further change the pharmacokinetic characteristics of some substrates of SULT2A1, and the activation of D1-like receptor is probably involved in rSULT2A1 induction by DA.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Guangping
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: tianyanzhou@bjmu.edu.cn.
authors.forename: Tianyan
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015153:Blotting, Western; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004790:Enzyme Induction; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D000077266:Moxifloxacin; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D000077266:Moxifloxacin; D004298:Dopamine
keywords: Dehydroepiandrosterone sulfotransferases (SULT2A1); Dopamine; Dopamine receptor; Induction; Liver; Moxifloxacin; Pharmacokinetics