Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4)
Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4)
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DOI：
10.1111/jnc.13758
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发表时间：
2016-11-01
影响因子：
4.7
通讯作者：
Hosoya, Ken-ichi
中科院分区：
文献类型：
--
作者：
Usui, Takuya;Nakazawa, Ayumi;Hosoya, Ken-ichi
在戊巴比妥钠麻醉的Wistar大鼠上，研究了组胺通过血脑屏障和血脑脊液屏障(BCSFB)从脑/脑脊液中清除的作用。一项活体脑内微量注射研究表明，[H-3]组胺只有部分从大鼠脑内流出穿过血脑屏障。[H-3]组胺从大鼠脑脊液中清除的清除量是脑脊液体积流动标记物的3.8倍，并且未标记组胺的联合给药显著抑制了[H-3]组胺的清除，这表明载体介导的过程参与了组胺从脑脊液中的清除。分离的大鼠脉络丛对[H-3]组胺的摄取研究表明，组胺通过BCSFB从脑脊液中消除。[H-3]组胺的摄取是BCSFB的模型细胞系，其摄取[H-3]组胺的动力学表现出温度依赖性和可饱和性，提示BCSFB参与了载体介导的组胺转运。在抑制研究中，[H-3]组胺摄取被质膜单胺转运体(pmAt/SLC29A4)底物和/或抑制剂显著抑制，但不受有机阳离子转运体底物的影响。这些结果表明，在BCSFB通过质膜单胺转运体从脑脊液中清除组胺。
The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF across the blood- brain barrier and bloodCSF barrier (BCSFB) was investigated using Wistar rats, which were anesthetized with pentobarbital sodium. An in vivo intracerebral microinjection study suggested that there was only partial efflux of [H-3] histamine from the rat brain across the blood- brain barrier. The [H-3] histamine elimination clearance from the rat CSF was 3.8- fold greater than that of a CSF bulk flow marker, and the elimination of [H-3] histamine was significantly inhibited by the co-administration of unlabeled histamine, suggesting the involvement of a carrier-mediated process in histamine elimination from the CSF. The uptake study of [H-3] histamine by the isolated rat choroid plexus revealed histamine elimination from the CSF across the BCSFB. The [H-3] histamine uptake by TR-CSFB3 cells, a model cell line for the BCSFB, exhibited temperaturedependent and saturable kinetics, suggesting the involvement of carrier-mediated transport of histamine at the BCSFB. In the inhibition study, [H-3] histamine uptake by TR-CSFB3 cells was significantly inhibited by substrates and/or inhibitors of plasma membrane monoamine transporter (PMAT/SLC29A4), but not affected by substrates of organic cation transporters. These results suggest the elimination of histamine from the CSF via plasma membrane monoamine transporter at the BCSFB.