title: Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5) in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model.
abstract: The aim of this study was to examine whether organic cation/carnitine transporter 2 (OCTN2/SLC22A5) plays a role in the human blood-brain barrier (BBB) by evaluating its functional activity in human brain endothelial cells (hCMEC/D3), which are considered to be a model of the BBB. The uptake of [(3)H]L-carnitine by hCMEC/D3 cells was time-, extracellular sodium- and concentration-dependent, with a Km value of 15.7 µM. These results are consistent with the properties of OCTN2-mediated L-carnitine transport. hCMEC/D3 cells showed relatively high expression of OCTN2 mRNA, and this expression was effectively decreased at 24-72 h after lipofection of cells with OCTN2 siRNA under optimized conditions. [(3)H]L-Carnitine uptake was dramatically suppressed by silencing of the OCTN2 gene. The inhibitory effect of OCTN2 gene silencing was similar to that of an excess amount of unlabeled L-carnitine. These results indicate that OCTN2 is involved in L-carnitine transport at the human BBB.
authors.affiliation: Laboratory of Drug Disposition & Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okura
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kato
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Deguchi
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000378:metabolism*; D002331:Carnitine / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine