Retinal transfer of nicotinate by H +-monocarboxylate transporter at the inner blood-retinal barrier

Masanori Tachikawa, Koji Murakami, Pamela Moore Martin, Ken Ichi Hosoya, Vadivel Ganapathy

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 [ 3H]-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 [ 3H]-nicotinate uptake by the retina was 5.4-fold greater than that of [ 14C]-sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled nicotinate and salicylate significantly decreased the in vivo retinal uptake of [ 3H]-nicotinate. [ 3H]-Nicotinate was taken up by TR-iBRB2 cells via an H +-dependent saturable process with a Michaelis constant of ~7mM. 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.

Original languageEnglish (US)
Pages (from-to)385-390
Number of pages6
JournalMicrovascular Research
Volume82
Issue number3
DOIs
StatePublished - Nov 1 2011

Fingerprint

Blood-Retinal Barrier
Niacin
Blood
Retina
Salicylates
Ibuprofen
Polymerase chain reaction
Coenzymes
Endothelial cells
Valproic Acid
Transcription
G-Protein-Coupled Receptors
Pyruvic Acid
NADP
Carotid Arteries
Pharmaceutical Preparations
NAD
Reverse Transcription
Blood Vessels
Sucrose

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Retinal transfer of nicotinate by H +-monocarboxylate transporter at the inner blood-retinal barrier. / Tachikawa, Masanori; Murakami, Koji; Martin, Pamela Moore; Hosoya, Ken Ichi; Ganapathy, Vadivel.

In: Microvascular Research, Vol. 82, No. 3, 01.11.2011, p. 385-390.

Research output: Contribution to journalArticle

Tachikawa, Masanori ; Murakami, Koji ; Martin, Pamela Moore ; Hosoya, Ken Ichi ; Ganapathy, Vadivel. / Retinal transfer of nicotinate by H +-monocarboxylate transporter at the inner blood-retinal barrier. In: Microvascular Research. 2011 ; Vol. 82, No. 3. pp. 385-390.
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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 [ 3H]-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 [ 3H]-nicotinate uptake by the retina was 5.4-fold greater than that of [ 14C]-sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled nicotinate and salicylate significantly decreased the in vivo retinal uptake of [ 3H]-nicotinate. [ 3H]-Nicotinate was taken up by TR-iBRB2 cells via an H +-dependent saturable process with a Michaelis constant of ~7mM. 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.",
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AB - 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 [ 3H]-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 [ 3H]-nicotinate uptake by the retina was 5.4-fold greater than that of [ 14C]-sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled nicotinate and salicylate significantly decreased the in vivo retinal uptake of [ 3H]-nicotinate. [ 3H]-Nicotinate was taken up by TR-iBRB2 cells via an H +-dependent saturable process with a Michaelis constant of ~7mM. 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.

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