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溶质载体家族6A转运体在血视网膜屏障和肝脏中牛磺酸生理转运中的作用

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood-Retinal Barrier and in the Liver.

作者信息

Kubo Yoshiyuki, Akanuma Shin-Ichi, Hosoya Ken-Ichi

机构信息

Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.

出版信息

Biol Pharm Bull. 2016;39(12):1903-1911. doi: 10.1248/bpb.b16-00597.

Abstract

Cumulative studies showed that taurine (2-aminoethanesulfonic acid) contributes to a variety of physiological events. Transport study suggested the cellular taurine transport in an Na- and Cl-dependent manner, and the several members of SLC6A family have been shown as taurine transporter. At the inner blood-retinal barrier (BRB), taurine transporter (TauT/SLC6A) is involved in the transport of taurine to the retina from the circulating blood. The involvement of TauT is also suggested in γ-aminobutyric acid (GABA) transport at the inner BRB, and its role is assumed in the elimination of GABA from the retinal interstitial fluid. In the retina, taurine is thought to be a major organic osmolyte, and its influx and efflux through TauT and volume-sensitive organic osmolyte and anion channel (VSOAC) in Müller cells regulate the osmolarity in the retinal microenvironment to maintain a healthy retina. In the liver, hepatocytes take up taurine via GABA transporter 2 (GAT2/SLC6A13, the orthologue of mouse GAT3) expressed at the sinusoidal membrane of periportal hepatocytes, contributing to the metabolism of bile acid. Site-directed mutagenesis study suggests amino acid residues that are crucial in the recognition of substrates by GATs and TauT. The evidence suggests the physiological impact of taurine transporters in tissues.

摘要

累积研究表明,牛磺酸(2-氨基乙磺酸)参与多种生理活动。转运研究表明,细胞内牛磺酸的转运依赖于钠离子和氯离子,并且SLC6A家族的几个成员已被证明是牛磺酸转运体。在内侧血视网膜屏障(BRB)处,牛磺酸转运体(TauT/SLC6A)参与将牛磺酸从循环血液转运至视网膜。TauT在内侧BRB处的γ-氨基丁酸(GABA)转运中也有作用,并且推测其在从视网膜间质液中清除GABA方面发挥作用。在视网膜中,牛磺酸被认为是一种主要的有机渗透溶质,其通过TauT以及Müller细胞中的容积敏感性有机渗透溶质和阴离子通道(VSOAC)的流入和流出调节视网膜微环境中的渗透压,以维持视网膜的健康。在肝脏中,肝细胞通过位于门静脉周围肝细胞窦状膜上表达的GABA转运体2(GAT2/SLC6A13,小鼠GAT3的同源物)摄取牛磺酸,这有助于胆汁酸的代谢。定点诱变研究表明了GATs和TauT识别底物时至关重要的氨基酸残基。证据表明牛磺酸转运体在组织中的生理影响。

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