Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites
Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites
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DOI：
10.1254/jphs.93.430
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发表时间：
2003-12-01
影响因子：
3.5
通讯作者：
Endou, H
中科院分区：
文献类型：
--
作者：
Alebouyeh, M;Takeda, M;Endou, H
本研究的目的是阐明人有机阴离子转运蛋白1（hOAT 1）和hOAT 3在人脑脉络丛的表达及其与神经递质代谢产物的相互作用，使用稳定的细胞系。免疫组织化学分析显示hOAT 1和hOAT 3表达于人脉络丛的细胞质膜和细胞质中。神经递质代谢产物，即5-甲氧基吲哚-3-乙酸（5-MI-3-AA）、高香草酸（HVA）、香草扁桃酸（VMA）、3，4-二羟基苯乙酸（DOPAC）、5 -羟基吲哚-3-乙酸（5-HI-3-AA），N-乙酰基-5-羟色胺（NA-5-HTT）、褪黑激素、5-甲氧基色胺（5-MTT）、3，4-二羟基扁桃酸（DHMA）、5-羟基扁桃醇和5-甲氧基扁桃醇（5-MTP），但不包括甲硫氨酸（MN）、去甲甲硫氨酸（NMN）、和3-甲基酪胺（3-MT），在2 mM，抑制对氨基马尿酸摄取介导的hOAT 1。另一方面，褪黑激素、5-MI-3-AA、NA-5-HTT、5-MTT、5-MTP、HVA、5-HI-3-AA、VMA、DOPAC、5-羟基山梨醇和MN（但不包括3-MT、DHMA和NMN）在2 mM时抑制hOAT 3介导的硫酸雌酮摄取。对于DHMA、DOPAC、HVA、5-HI-3-AA、褪黑激素、5-MI-3-AA、5-MTP、5-MTT和VMA，观察到hOAT 1和hOAT 3之间IC 50值的差异。HOAT 1和hOAT 3介导VMA的转运，但不介导HVA和褪黑素的转运。这些结果表明，hOAT 1和hOAT 3参与了各种神经递质代谢物从脑脊液穿过脉络丛流出到血液中。
The purpose of the present study was to elucidate the expression of human organic anion transporter 1 (hOAT1) and hOAT3 in the choroid plexus of the human brain and their interactions with neurotransmitter metabolites using stable cell lines. Immunohistochemical analysis revealed that hOAT1 and hOAT3 are expressed in the cytoplasmic membrane and cytoplasm of human choroid plexus. Neurotransmitter metabolites, namely, 5-methoxyindole-3-acetic acid (5-MI-3-AA), homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5 -hydroxyindole-3-acetic acid (5-HI-3-AA), N-acetyl-5-hydroxytryptamine (NA-5-HTT), melatonin, 5-methoxytryptamine (5-MTT), 3,4-dihidroxymandelic acid (DHMA), 5-hydroxytryptophol, and 5-methoxytryptophol (5-MTP), but not methanephrine (MN), normethanephrine (NMN), and 3-methyltyramine (3-MT), at 2 mM, inhibited para-aminohippuric acid uptake mediated by hOAT1. On the other hand, melatonin, 5-MI-3-AA, NA-5-HTT, 5-MTT, 5-MTP, HVA, 5-HI-3-AA, VMA, DOPAC, 5-hydroxytryptophol, and MN, but not 3-MT, DHMA, and NMN, at 2 mM, inhibited estrone sulfate uptake mediated by hOAT3. Differences in the IC50 values between hOAT1 and hOAT3 were observed for DHMA, DOPAC, HVA, 5-HI-3-AA, melatonin, 5-MI-3-AA, 5-MTP, 5-MTT, and VMA. HOAT1 and hOAT3 mediated the transport of VMA but not HVA and melatonin. These results suggest that hOAT1 and hOAT3 are involved in the efflux of various neurotransmitter metabolites from the cerebrospinal fluid to the blood across the choroid plexus.