title: Organic anion transporting polypeptide 2 transports valproic acid in rat brain microvascular endothelial cells.
abstract: OBJECTIVE
  Abnormal drug transporter expression or function in the brain may lead to decreased concentrations of antiepileptic drugs (AEDs) in the central nervous system in patients with drug-resistant epilepsy. We previously showed the influx transporter organic anion transport polypeptide 2 (Oatp2) was expressed in rat brain microvascular endothelial cells (BMECs). Seizures decrease expression of Oatp2, but it remains unclear whether Oatp2 transports AEDs. In this study, we utilized rat BMECs as an in vitro model of the blood-brain barrier (BBB) to study Oatp2-mediated transport of valproic acid (VPA), the most common clinically used AEDs.
  
  
  METHODS
  In vivo injection of pregnenolone-16-carbonitrile was used to induce high expression of Oatp2 in isolated BMECs. Small interfering RNA treatment was used to silence Oatp2, and uptake of VPA was assessed.
  
  
  RESULTS
  Increased expression of Oatp2 in BMECs increased the uptake of VPA, while inhibition of Oatp2 reduced VPA uptake.
  
  
  CONCLUSIONS
  This study indicates Oatp2 transports VPA across the BBB, and suggests altered Oatp2 expression may contribute to resistance to VPA in patients with drug-resistant epilepsy.
authors.affiliation: a Department of Neurology , Children's Hospital of Chongqing Medical University , Chongqing , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: a Department of Neurology , Children's Hospital of Chongqing Medical University , Chongqing , China.|b Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing , Chongqing International Science and Technology Cooperation Center for Child Development and Disorders , Chongqing , China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D055806:Microvessels / Q000166:cytology*; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D011284:Pregnenolone / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014635:Valproic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C546977:AR C155858; D000097:Acetonitriles; D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C503597:Slco1a4 protein, rat; D013876:Thiophenes; C071461:pregnenolone 16-acetonitrile; D014498:Uracil; D014635:Valproic Acid; D011284:Pregnenolone
keywords: Brain microvascular endothelial cells; Drug transport; Organic anion transporting polypeptide 2; Valproate