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Characterization of monocarboxylate uptake and immunohistochemical demonstration of monocarboxylate transporters in cultured rabbit corneal epithelial cells



Kouichi Kawazu, Santen Pharmaceutical Co., Ltd, Nara Research and Development Center, 8916-16 Takayama-cho, Ikoma-shi 630-0101, Japan.




This study aimed to characterize the mechanisms of monocarboxylate uptake by cultured rabbit corneal epithelial cells (RCECs) using l- and d-lactic acids as model substrates.


l-/d-Lactic acid uptake was evaluated by measuring the accumulation in confluent RCECs. Also, we demonstrated the distribution of monocarboxylate transporters (MCTs) in RCECs by immunohistochemistry.

Key findings

The accumulation of 14C-labelled l- and d-lactic acids was dependent on time, pH and temperature. The Arrhenius plots of the uptake were biphasic. The initial uptake of 14C-labelled l-lactic acid exhibited concentration dependence and was greater than that of the d-isomer. The initial uptake of 14C-labelled l- and d-lactic acids involved saturable and nonsaturable processes; the saturable process exhibited higher affinity for l-lactic acid than for the d-isomer. l-/d-lactic acid uptake was inhibited by chiral monocarboxylate in a stereoselective manner. The uptake of 14C-labelled l- and d-lactic acids was sensitive to metabolic inhibitors and other monocarboxylates. MCT expression in RCECs was confirmed immunohistochemically. In particular, MCT2 expression was detected in RCECs, whereas MCT1, MCT4 and MCT5 expression was detected in the surface layer.


These results indicate that the carrier-mediated transport system specific for monocarboxylates elicits lactic acid uptake in RCECs. Therefore, the transcorneal permeation of drugs with a monocarboxylic moiety may be dependent on the activity of a specific pH-dependent transporter as well as passive diffusion according to the pH-partition theory.