tailieunhanh - Báo cáo khoa học: The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters

The bioactive dipeptide derivative anserine (b-alanyl-1-N-methyl-l-histidine) is absorbed from the human diet in intact form at the intestinal epithelium. The purpose of this study was to investigate whether anserine is a substrate of the H + ⁄peptide cotransporters 1 and 2 (PEPT1 and PEPT2). | ễFEBS Journal The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters Stefanie Geissler1 Madlen Zwarg1 Ilka Kniitter1 Fritz Markwardt2 and Matthias Brandsch1 1 Membrane Transport Group Biozentrum of Martin-Luther-University Halle-Wittenberg Halle Germany 2 Julius-Bernstein-Institute for Physiology Martin-Luther-University Halle-Wittenberg Halle Germany Keywords carnosine intestine kidney PEPT1 PEPT2 Correspondence M. Brandsch Membrane Transport Group Biozentrum of Martin-Luther-University Halle-Wittenberg Weinbergweg 22 D-06120 Halle Germany Fax 49 345 5527258 Tel 49 345 5521630 E-mail . Received 4 November 2009 revised 2 December 2009 accepted 2 December 2009 doi The bioactive dipeptide derivative anserine b-alanyl-1-N-methyl-L-histidine is absorbed from the human diet in intact form at the intestinal epithelium. The purpose of this study was to investigate whether anserine is a substrate of the H peptide cotransporters 1 and 2 PEPT1 and PEPT2 . We first assessed the effects of anserine on 14C glycylsarcosine 14C Gly-Sar uptake into Caco-2 cells expressing human PEPT1 and into spontaneous hypertensive rat kidney proximal tubule SKPT cells expressing rat PEPT2. Anserine inhibited 14C Gly-Sar uptake with Ki values of mM Caco-2 and mM SKPT . In HeLa cells transfected with pcDNA3-hPEPT1 or pcDNA3-hPEPT2 Ki values of mM hPEPT1 and mM hPEPT2 were obtained. We conclude from these data that anserine is recognized by PEPT1 and PEPT2. Carnosine also inhibited 14C Gly-Sar uptake. Using the two-electrode voltage-clamp technique at Xenopus laevis oocytes strong hPEPT1-specific inward transport currents were recorded for Gly-Sar anserine and carnosine but not for glycine. We conclude that anserine and carnosine interact with the human intestinal peptide transporter and are transported by hPEPT1 in an active electrogenic H symport. As PEPT1 is the .