Groneberg David A, Döring Frank, Theis Stephan, Nickolaus Monika, Fischer Axel, Daniel Hannelore
Dept. of Pediatric Pneumology and Immunology, Charité Campus-Virchow, Humboldt-University, D-13353 Berlin, Germany.
Am J Physiol Endocrinol Metab. 2002 May;282(5):E1172-9. doi: 10.1152/ajpendo.00381.2001.
The lactating mammary gland utilizes free plasma amino acids as well as those derived by hydrolysis from circulating short-chain peptides for protein synthesis. Apart from the major route of amino acid nitrogen delivery to the gland by the various transporters for free amino acids, it has been suggested that dipeptides may also be taken up in intact form to serve as a source of amino acids. The identification of peptide transporters in the mammary gland may therefore provide new insights into protein metabolism and secretion by the gland. The expression and distribution of the high-affinity type proton-coupled peptide transporter PEPT2 were investigated in rat lactating mammary gland as well as in human epithelial cells derived from breast milk. By use of RT-PCR, PEPT2 mRNA was detected in rat mammary gland extracts and human milk epithelial cells. The expression pattern of PEPT2 mRNA revealed a localization in epithelial cells of ducts and glands by nonisotopic high resolution in situ hybridization. In addition, immunohistochemistry was carried out and showed transporter immunoreactivity in the same epithelial cells of the glands and ducts. In addition, two-electrode voltage clamp recordings using PEPT2-expressing Xenopus laevis oocytes demonstrated positive inward currents induced by selected dipeptides that may play a role in aminonitrogen handling in mammalian mammary gland. Taken together, these data suggest that PEPT2 is expressed in mammary gland epithelia, in which it may contribute to the reuptake of short-chain peptides derived from hydrolysis of milk proteins secreted into the lumen. Whereas PEPT2 also transports a variety of drugs, such as selected beta-lactams, angiotensin-converting enzyme inhibitors, and antiviral and anticancer metabolites, their efficient reabsorption via PEPT2 may reduce the burden of xenobiotics in milk.
泌乳期乳腺利用游离血浆氨基酸以及通过循环短链肽水解产生的氨基酸进行蛋白质合成。除了各种游离氨基酸转运蛋白将氨基酸氮输送到乳腺的主要途径外，有人提出二肽也可能以完整形式被摄取，作为氨基酸的来源。因此，乳腺中肽转运蛋白的鉴定可能为该腺体的蛋白质代谢和分泌提供新的见解。研究了高亲和力质子偶联肽转运蛋白PEPT2在大鼠泌乳期乳腺以及母乳来源的人上皮细胞中的表达和分布。通过逆转录聚合酶链反应（RT-PCR），在大鼠乳腺提取物和人乳上皮细胞中检测到了PEPT2信使核糖核酸（mRNA）。通过非同位素高分辨率原位杂交，PEPT2 mRNA的表达模式显示其定位于导管和腺体的上皮细胞中。此外，进行了免疫组织化学检测，结果显示在腺体和导管的相同上皮细胞中有转运蛋白免疫反应性。此外，使用表达PEPT2的非洲爪蟾卵母细胞进行的双电极电压钳记录表明，所选二肽可诱导正向内向电流，这可能在哺乳动物乳腺的氨基氮处理中发挥作用。综上所述，这些数据表明PEPT2在乳腺上皮细胞中表达，它可能有助于重新摄取源自分泌到管腔中的乳蛋白水解产生的短链肽。虽然PEPT2也转运多种药物，如所选的β-内酰胺类、血管紧张素转换酶抑制剂以及抗病毒和抗癌代谢物，但通过PEPT2对它们的有效重吸收可能会减轻牛奶中异生素的负担。
