Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type and Pept1 Knockout Mice
Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type and Pept1 Knockout Mice
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DOI：
10.1124/dmd.110.034025
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Smith, David E.
中科院分区：
文献类型：
--
作者：
Jappar, Dilara;Wu, Shu-Pei;Smith, David E.
本研究的目的是评估的作用，相关性和区域依赖性的肽转运蛋白（PEPT）1的表达和功能在小鼠肠道使用的模型二肽甘氨酰肌氨酸（GlySar）。在分离特定肠段后，在野生型和Pept 1敲除小鼠中进行原位单程灌注。测量[H-3]GlySar的渗透性作为灌流液pH、二肽浓度、潜在抑制剂和肠段的函数，沿着PEPT 1 mRNA和蛋白。我们发现GlySar的渗透性是可饱和的（Km = 5.7 mM），pH依赖性（在pH 5.5时最大值），并且对PEPT 1具有特异性;其他肽转运蛋白，如PHT 1和PHT 2，不参与，这是通过过量浓度的组氨酸缺乏GlySar抑制来判断的。GlySar渗透性在野生型小鼠的十二指肠和空肠中相当，但远大于回肠中的渗透性（约2倍）。在野生型小鼠的结肠中没有观察到PEPT 1介导的GlySar渗透性（
The purpose of this study was to evaluate the role, relevance, and regional dependence of peptide transporter (PEPT) 1 expression and function in mouse intestines using the model dipeptide glycylsarcosine (GlySar). After isolating specific intestinal segments, in situ single-pass perfusions were performed in wild-type and Pept1 knockout mice. The permeability of [H-3]GlySar was measured as a function of perfusate pH, dipeptide concentration, potential inhibitors, and intestinal segment, along with PEPT1 mRNA and protein. We found the permeability of GlySar to be saturable (K-m = 5.7 mM), pH-dependent (maximal value at pH 5.5), and specific for PEPT1; other peptide transporters, such as PHT1 and PHT2, were not involved, as judged by the lack of GlySar inhibition by excess concentrations of histidine. GlySar permeabilities were comparable in the duodenum and jejunum of wild-type mice but were much larger than that in ileum (approximately 2-fold). A PEPT1-mediated permeability was not observed for GlySar in the colon of wild-type mice (