Monocarboxylate transport in human corneal epithelium and cell lines.
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.
Vellonen
Kati-Sisko
KS
Centre for Drug Research, University of Helsinki, Helsinki, Finland. Kati-Sisko.Vellonen@helsinki.fi
Häkli
Marika
M
Merezhinskaya
Natalya
N
Tervo
Timo
T
Honkakoski
Paavo
P
Urtti
Arto
A
D000042:Absorption; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D010539:Permeability; D011817:Rabbits; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C106260:SLC16A3 protein, human; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human