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人眼角膜上皮和细胞系中的单羧酸转运。

Monocarboxylate transport in human corneal epithelium and cell lines.

机构信息

Centre for Drug Research, University of Helsinki, Helsinki, Finland.

出版信息

Eur J Pharm Sci. 2010 Feb 19;39(4):241-7. doi: 10.1016/j.ejps.2009.12.006. Epub 2009 Dec 24.

Abstract

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.

摘要

单羧酸转运蛋白(MCTs)是能够穿过细胞膜转运乳酸和其他内源性和外源性单羧酸的跨膜蛋白。本研究旨在评估人 MCT1、MCT3 和 MCT4 在角膜上皮、角膜上皮细胞系(原代 HCEpiC 和永生化 HCE 细胞)和分离的兔角膜中的表达和转运体作用。MCT1 和 MCT4 在人角膜上皮和细胞系中均在 mRNA 和蛋白水平上表达。细胞摄取研究表明,L-乳酸的摄取是可饱和的且依赖于 pH,这一过程可被各种单羧酸如双氯芬酸和氟比洛芬所抑制。苯甲酸在兔角膜中的通透性在吸收方向上更高,而在存在单羧酸药物丙戊酸钠的情况下,这种方向性降低。单羧酸转运在人角膜上皮细胞和兔角膜中具有功能,它可能在眼部药物吸收中发挥作用。

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