Ford Dianne, Howard Alison, Hirst Barry H
School of Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
Histochem Cell Biol. 2003 Jan;119(1):37-43. doi: 10.1007/s00418-002-0479-y. Epub 2002 Dec 10.
Substrates of the proton-coupled peptide transporter, hPepT1, include dietary di- and tripeptides plus therapeutically important drugs such as the beta-lactam antibiotics and angiotensin-converting enzyme inhibitors. Expression and function of hPepT1 in the small bowel is well established. We have compared levels of hPepT1 mRNA expression in regions of human gut by RT-PCR methods and examined the expression of hPepT1 in normal human colon using an anti-hPepT1 antipeptide antibody. hPepT1 mRNA was expressed in the large intestine, although at lower levels than in the small intestine. Quantitatively, expression in ileum was 4.6-fold greater than in sigmoid colon. Immunoreactive hPepT1 was detected in human colon at lower levels than in ileum. The pattern of expression differed between the two tissues: whilst expression in the ileum was localised to the apical enterocyte membrane along the length of the crypt-villus axis, expression in the colonocyte was detected at the apical membrane towards the luminal surface but predominantly at the basal membrane towards the base of the crypt. We conclude that distal regions of the bowel express hPepT1, which may provide a mechanism for colonic protein-nitrogen absorption and for absorption of therapeutically important peptidomimetic drugs.
质子偶联肽转运体hPepT1的底物包括膳食二肽和三肽以及具有重要治疗意义的药物,如β-内酰胺类抗生素和血管紧张素转换酶抑制剂。hPepT1在小肠中的表达和功能已得到充分证实。我们通过逆转录聚合酶链反应(RT-PCR)方法比较了人肠道各区域hPepT1 mRNA的表达水平,并使用抗hPepT1抗肽抗体检测了正常人类结肠中hPepT1的表达。hPepT1 mRNA在大肠中表达,但其水平低于小肠。定量分析显示,回肠中的表达比乙状结肠高4.6倍。在人类结肠中检测到的免疫反应性hPepT1水平低于回肠。两种组织中的表达模式有所不同:回肠中的表达沿隐窝-绒毛轴全长定位于顶端肠细胞膜,而结肠细胞中的表达在朝向管腔表面的顶端膜上检测到,但主要在朝向隐窝底部的基底膜上。我们得出结论,肠道远端区域表达hPepT1,这可能为结肠蛋白质-氮的吸收以及治疗上重要的拟肽药物的吸收提供一种机制。