Retinal transfer of nicotinate by H+ -monocarboxylate transporter at the inner blood-retinal barrier.
Retinal transfer of nicotinate by H+ -monocarboxylate transporter at the inner blood-retinal barrier.
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DOI：
10.1016/j.mvr.2011.06.009
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发表时间：
2011-11
影响因子：
3.1
通讯作者：
Ganapathy V
中科院分区：
文献类型：
--
作者：
Tachikawa M;Murakami K;Martin PM;Hosoya K;Ganapathy V
烟酸是辅酶NAD和NADP的组成部分。它也是G蛋白偶联受体GPR 109 A的激动剂。烟酸被广泛用作高剂量的降脂药物，这与称为烟酸黄斑病变的眼部副作用有关。在这里，我们研究了烟酸酯通过血视网膜屏障（BRB）转移到视网膜的机制。采用颈动脉注射技术研究了[3 H]-烟酸盐在体内的血液-视网膜转运。在条件永生化的大鼠视网膜毛细血管内皮细胞系（TR-iBRB 2），在体外模型的内部BRB的烟酸转运的特点进行了研究。逆转录-聚合酶链反应检测TR-iBRB 2细胞中转运蛋白的表达。在体内[3 H]-烟酸吸收的视网膜是5.4倍大于[14 C]-蔗糖，BRB不渗透的血管空间标记。过量的未标记烟酸盐和水杨酸盐显着降低体内视网膜摄取[3 H]-烟酸盐。TR-iBRB 2细胞通过H+依赖性饱和过程摄取[3 H]-烟酸盐，米氏常数约为7 mM。Na+对摄取的影响极小。内源性单羧酸盐（如乳酸盐和丙酮酸盐）和单羧酸药物（如丙戊酸盐、水杨酸盐和布洛芬）可显著抑制H+依赖性摄取。这些特征与H+偶联单羧酸转运蛋白（MCT）的特征一致。MCT 1、MCT 2和MCT 4 mRNA在TR-iBRB 2细胞中表达。Na+依赖性单羧酸转运蛋白SMCT 1和SMCT 2在这些细胞中不表达。总之，烟酸酯从血液转移到视网膜通过内部BRB发生主要是通过H+耦合monocarbxylate转运。
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 ~7 mM. Na+ had minimal effect on the uptake. The H+-dependent uptake was significantly inhibited by endogenous monocarboxylates such as lactate and puruvate, 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 monocarbxylate transporters.
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影响因子：
3.4
作者：
Hosoya, K;Tomi, M;Terasaki, T
通讯作者：
Terasaki, T
影响因子：
3.7
作者：
Hosoya, Ken-ichi;Yamamoto, Atsushi;Tachikawa, Masanori
通讯作者：
Tachikawa, Masanori
影响因子：
8.9
作者：
HENDERSON, LM
通讯作者：
HENDERSON, LM
影响因子：
2.1
作者：
ALM, A;TORNQUIST, P
通讯作者：
TORNQUIST, P
影响因子：
3.7
作者：
Hosoya, K;Kondo, T;Terasaki, T
通讯作者：
Terasaki, T