Functional Expression of Carnitine/Organic Cation Transporter 1 in Murine Choroid Plexus.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI:10.1248/bpb.b24-00451
Takahiro Ishimoto, Noritaka Nakamichi, Takayuki Taguchi, Misa Nishiyama, Yukio Kato
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Abstract

Membrane transporters expressed in the choroid plexus (CP) are involved in the transport of substances between the blood and cerebrospinal fluid (CSF). Carnitine/organic cation transporter 1 (OCTN1, also known as SLC22A4) is expressed in rodent CP; however, its specific roles in blood-CSF transport remain unclear. Therefore, in this study, we aimed to evaluate the potential role of OCTN1 in the elimination of substances from CSF. Tritium-labeled ergothioneine ([3H]ERGO), a typical in vivo substrate of OCTN1, was injected into the lateral ventricles of wild-type and octn1 gene knockout (octn1-/-) mice. Clearance of [3H]ERGO from CSF was higher than that of the bulk flow marker, [14C]mannitol, in wild-type mice. However, [3H]ERGO clearance was significantly lower in octn1-/- mice than in wild-type mice. Furthermore, OCTN1 expression in CP was determined via immunohistochemical analysis. CP/CSF ratio of [3H]ERGO was significantly lower in octn1-/- mice than in wild-type mice. These results suggest that OCTN1 is functionally expressed in CP and involved in the elimination of ERGO from CSF in mice.

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肉碱/有机阳离子转运体 1 在小鼠脉络丛中的功能表达
脉络丛(CP)中表达的膜转运体参与了血液和脑脊液(CSF)之间的物质转运。肉碱/有机阳离子转运体 1(OCTN1,又称 SLC22A4)在啮齿类动物的脉络丛中表达,但它在血液-脑脊液转运中的具体作用仍不清楚。因此,在本研究中,我们旨在评估 OCTN1 在从 CSF 中清除物质方面的潜在作用。将氚标记的麦角硫因([3H]ERGO)(一种典型的 OCTN1 体内底物)注入野生型小鼠和 octn1 基因敲除(octn1-/-)小鼠的侧脑室。野生型小鼠脑脊液中[3H]ERGO的清除率高于大量流动标记物[14C]甘露醇的清除率。然而,octn1-/-小鼠的[3H]ERGO清除率明显低于野生型小鼠。此外,通过免疫组化分析确定了 CP 中 OCTN1 的表达。octn1-/-小鼠体内[3H]ERGO的CP/CSF比值明显低于野生型小鼠。这些结果表明,OCTN1 在小鼠 CP 中有功能性表达,并参与清除 CSF 中的 ERGO。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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