Document Detail


Characterization of monocarboxylate uptake and immunohistochemical demonstration of monocarboxylate transporters in cultured rabbit corneal epithelial cells.
MedLine Citation:
PMID:  23356841     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: 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.
METHODS: 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 (14) C-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 (14) C-labelled l-lactic acid exhibited concentration dependence and was greater than that of the d-isomer. The initial uptake of (14) C-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 (14) C-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.
CONCLUSION: 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.
Authors:
Kouichi Kawazu; Shinobu Fujii; Kazuhito Yamada; Katsuhiko Shinomiya; Osamu Katsuta; Yoshihide Horibe
Publication Detail:
Type:  Journal Article     Date:  2012-11-01
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  65     ISSN:  2042-7158     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  328-36     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.
Affiliation:
Nara Research and Development Center, Santen Pharmaceutical Co., Ltd, Nara, Japan.
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