Monocarboxylate transport in human corneal epithelium and cell lines

被引:28
作者
Vellonen, Kati-Sisko [1 ,2 ,3 ]
Hakli, Marika [1 ]
Merezhinskaya, Natalya [4 ]
Tervo, Timo [5 ]
Honkakoski, Paavo [3 ]
Urtti, Arto [1 ]
机构
[1] Univ Helsinki, Ctr Drug Res, Fac Pharm, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Div Biopharmaceut & Pharmacokinet, FIN-00014 Helsinki, Finland
[3] Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland
[4] Armed Forces Inst Pathol, Div Environm Toxicol, Environm & Infect Dis Sci Dept, Washington, DC 20306 USA
[5] Univ Helsinki, Dept Ophthalmol, FIN-00014 Helsinki, Finland
基金
芬兰科学院;
关键词
Corneal epithelium; Monocarboxylate transporter; MCT; SLC16; Ocular absorption; Ophthalmic drugs; CARRIER-MEDIATED TRANSPORT; ACID TRANSPORTERS; SKELETAL-MUSCLE; TISSUES; EXPRESSION; LACTATE; FAMILY; MCT2; LOCALIZATION; DELIVERY;
D O I
10.1016/j.ejps.2009.12.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Monocarboxylate transporters (MCTs) are transmembrane proteins capable of transferring lactate and other endogenous and exogenous monocarboxylates across the cell membrane. The aim of the present study was to assess the expression and transporter role of human MCT1, MCT3 and MCT4 in the corneal epithelium, corneal epithelial cell lines (primary HCEpiC and immortalized HCE cells) and isolated rabbit corneas. MCT1 and MCT4 were expressed in the human corneal epithelium and the cell lines at mRNA and protein levels. Cellular uptake studies showed saturable and pH-dependent L-lactic acid transport, which was inhibited by various monocarboxylates like diclofenac and flurbiprofen. The permeability of benzoic acid across the rabbit cornea was higher in absorptive direction and this directionality was diminished in the presence of monocarboxylate drug valproic acid. Monocarboxylate transport was functional in the human corneal epithelial cells and rabbit cornea and it may play a role in the ocular drug absorption. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:241 / 247
页数:7
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