alexa Retinal transfer of nicotinate by H+ -monocarboxylate transporter at the inner blood-retinal barrier.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Computer Science & Systems Biology

Author(s): Tachikawa M, Murakami K, Martin PM, Hosoya K, Ganapathy V

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Abstract Nicotinic acid is a constituent of the coenzymes NAD and NADP. It also serves as an agonist for the G-protein-coupled receptor GPR109A. Nicotinic acid is widely used at high doses as a lipid-lowering drug, which is associated with an ocular side effect known as niacin maculopathy. Here we investigated the mechanism by which nicotinate is transferred into retina across the inner blood-retinal barrier (BRB). In vivo the blood-to-retina transport of [(3)H]-nicotinate was studied using the carotid artery injection technique. The characteristics of nicotinate transport at the inner BRB were examined in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2), an in vitro model of inner BRB. The expression of transporters in TR-iBRB2 cells was determined by reverse transcription-polymerase chain reaction. In vivo [(3)H]-nicotinate uptake by the retina was 5.4-fold greater than that of [(14)C]-sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled nicotinate and salicylate significantly decreased the in vivo retinal uptake of [(3)H]-nicotinate. [(3)H]-Nicotinate was taken up by TR-iBRB2 cells via an H(+)-dependent saturable process with a Michaelis constant of ~7 mM. Na(+) had minimal effect on the uptake. The H(+)-dependent uptake was significantly inhibited by endogenous monocarboxylates such as lactate and pyruvate, and monocarboxylic drugs such as valproate, salicylate, and ibuprofen. These characteristics are consistent with those of H(+)-coupled monocarboxylate transporters (MCTs). MCT1, MCT2, and MCT4 mRNAs were expressed in TR-iBRB2 cells. The Na(+)-dependent monocarboxylate transporters SMCT1 and SMCT2 were not expressed in these cells. In conclusion, transfer of nicotinate from blood to retina across the inner BRB occurs primarily via H(+)-coupled monocarboxylate transporters. Copyright © 2011. Published by Elsevier Inc.
This article was published in Microvasc Res and referenced in Journal of Computer Science & Systems Biology

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