Anderson Catriona M H, Howard Alison, Walters Julian R F, Ganapathy Vadivel, Thwaites David T
Epithelial Research Group, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
J Physiol. 2009 Feb 15;587(Pt 4):731-44. doi: 10.1113/jphysiol.2008.164228. Epub 2008 Dec 15.
Taurine is an essential amino acid in some mammals and is conditionally essential in humans. Taurine is an abundant component of meat and fish-based foods and has been used as an oral supplement in the treatment of disorders such as cystic fibrosis and hypertension. The purpose of this investigation was to identity the relative contributions of the solute transporters involved in taurine uptake across the luminal membrane of human enterocytes. Distinct transport characteristics were revealed following expression of the candidate solute transporters in Xenopus laevis oocytes: PAT1 (SLC36A1) is a H(+)-coupled, pH-dependent, Na(+)- and Cl(-)-independent, low-affinity, high-capacity transporter for taurine and beta-alanine; TauT (SLC6A6) is a Na(+)- and Cl(-)-dependent, high-affinity, low-capacity transporter of taurine and beta-alanine; ATB(0,+) (SLC6A14) is a Na(+)- and Cl(-)-dependent, high-affinity, low-capacity transporter which accepts beta-alanine but not taurine. Taurine uptake across the brush-border membrane of human intestinal Caco-2 cell monolayers showed characteristics of both PAT1- and TauT-mediated transport. Under physiological conditions, Cl(-)-dependent TauT-mediated uptake predominates at low taurine concentrations, whereas at higher concentrations typical of diet, Cl(-)-independent PAT1-mediated uptake is the major absorptive mechanism. Real-time PCR analysis of human duodenal and ileal biopsy samples demonstrates that PAT1, TauT and ATB(0,+) mRNA are expressed in each tissue but to varying degrees. In conclusion, this study is the first to demonstrate both taurine uptake via PAT1 and functional coexpression of PAT1 and TauT at the apical membrane of the human intestinal epithelium. PAT1 may be responsible for bulk taurine uptake during a meal whereas TauT may be important for taurine supply to the intestinal epithelium and for taurine capture between meals.
牛磺酸在一些哺乳动物中是必需氨基酸,在人类中为条件必需氨基酸。牛磺酸是肉类和鱼类食品中的丰富成分,已被用作口服补充剂来治疗诸如囊性纤维化和高血压等疾病。本研究的目的是确定参与牛磺酸跨人肠上皮细胞腔面膜摄取的溶质转运体的相对贡献。在非洲爪蟾卵母细胞中表达候选溶质转运体后,揭示了不同的转运特性:PAT1(SLC36A1)是一种H⁺偶联、pH依赖性、不依赖Na⁺和Cl⁻、低亲和力、高容量的牛磺酸和β-丙氨酸转运体;TauT(SLC6A6)是一种依赖Na⁺和Cl⁻、高亲和力、低容量的牛磺酸和β-丙氨酸转运体;ATB(0,+)(SLC6A14)是一种依赖Na⁺和Cl⁻、高亲和力、低容量的转运体,它接受β-丙氨酸但不接受牛磺酸。牛磺酸跨人肠Caco-2细胞单层刷状缘膜的摄取表现出PAT1和TauT介导转运的特征。在生理条件下,低牛磺酸浓度时,依赖Cl⁻的TauT介导的摄取占主导,而在饮食中典型的较高浓度时,不依赖Cl⁻的PAT1介导的摄取是主要的吸收机制。对人十二指肠和回肠活检样本的实时PCR分析表明,PAT1、TauT和ATB(0,+) mRNA在每个组织中均有表达,但程度不同。总之,本研究首次证明了通过PAT1摄取牛磺酸以及PAT1和TauT在人肠上皮顶端膜上的功能性共表达。PAT1可能负责进食期间大量牛磺酸的摄取,而TauT可能对向肠上皮供应牛磺酸以及餐间捕获牛磺酸很重要。