title: Identification of the Human SULT Enzymes Involved in the Metabolism of Rotigotine.
abstract: Sulfation has been reported to be a major pathway for the metabolism and inactivation of rotigotine in vivo. The current study aimed to identify the human cytosolic sulfotransferase (SULT) enzyme(s) capable of mediating the sulfation of rotigotine. Of the 13 known human SULTs examined, 6 of them (SULT1A1, 1A2, 1A3, 1B1, 1C4, 1E1) displayed significant sulfating activities toward rotigotine. pH dependence and kinetic parameters of the sulfation of rotigotine by relevant human SULTs were determined. Of the 6 human organ samples tested, small intestine and liver cytosols displayed considerably higher rotigotine-sulfating activity than did brain, lung, and kidney. Moreover, sulfation of rotigotine was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under metabolic conditions. Collectively, the results obtained provided a molecular basis underlying the previous finding of the excretion of sulfated rotigotine by patients undergoing treatment with rotigotine.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.|Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.|School of Pharmacy, North Sichuan Medical College, Nan Chong, Sichuan, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
authors.affiliation: Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Juming
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.|School of Pharmacy, North Sichuan Medical College, Nan Chong, Sichuan, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D018938:Caco-2 Cells; D018491:Dopamine Agonists / Q000378:metabolism* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D015238:Sulfotransferases / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism* / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism* / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D015238:Sulfotransferases
keywords: SULT; cytosolic sulfotransferase; rotigotine; sulfation