Targeted disruption of organic cation transporter 3 (Oct3) ameliorates ischemic brain damage through modulating histamine and regulatory T cells

Pengxiang Zhu, Ryuji Hata, Masahito Ogasawara, Fang Cao, Kenji Kameda, Kohei Yamauchi, Alfred H. Schinkel, Kazutaka Maeyama, Masahiro Sakanaka

研究成果: Article査読

18 被引用数 (Scopus)

抄録

The organic cation transporters OCT1, 2, and 3 (SLC22A1-3) have been implicated in the elimination of biogenic amines such as histamine. Among them, OCT3 was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of organic cation transporter-3 (Oct3) on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild-type (Wt) littermates. Although targeted disruption of Oct3 did not affect physiological parameters after MCA occlusion, this disruption significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, targeted disruption of Oct3 prevented the reduction of regulatory T-cell proportion after cerebral ischemia while this disruption did not affect Th1 and Th2 cells proportions after ischemia. Since repeated administration of L-histidine (a precursor of histamine) to Wt mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of Oct3 ameliorated ischemic brain damage through an increase in regulatory T cells.

本文言語English
ページ(範囲)1897-1908
ページ数12
ジャーナルJournal of Cerebral Blood Flow and Metabolism
32
10
DOI
出版ステータスPublished - 10-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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