Mooij Miriam G, de Koning Barbara E A, Lindenbergh-Kortleve Dicky J, Simons-Oosterhuis Ytje, van Groen Bianca D, Tibboel Dick, Samsom Janneke N, de Wildt Saskia N
Intensive Care and Department of Pediatric Surgery (M.G.M., B.E.A.K., B.D.G., D.T., S.N.W.), and Department of Pediatrics (D.J.L.-K., Y.S.-O., J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; and Department of Pharmacology and Toxicology, Radboudumc, Nijmegen, The Netherlands (S.N.W.).
Intensive Care and Department of Pediatric Surgery (M.G.M., B.E.A.K., B.D.G., D.T., S.N.W.), and Department of Pediatrics (D.J.L.-K., Y.S.-O., J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; and Department of Pharmacology and Toxicology, Radboudumc, Nijmegen, The Netherlands (S.N.W.)
Drug Metab Dispos. 2016 Jul;44(7):1014-9. doi: 10.1124/dmd.115.068809. Epub 2016 Apr 14.
The intestinal influx oligopeptide transporter peptide transporter 1 (PEPT1) (SLC15A1) is best known for nutrient-derived di- and tripeptide transport. Its role in drug absorption is increasingly recognized. To better understand the disposition of PEPT1 substrate drugs in young infants, we studied intestinal PEPT1 mRNA expression and tissue localization across the pediatric age range. PEPT1 mRNA expression was determined using real-time reverse-transcription polymerase chain reaction in small intestinal tissues collected from surgical procedures (neonates and infants) or biopsies (older children and adolescents). PEPT1 mRNA relative to villin mRNA expression was compared between neonates/infants and older children/adolescents. PEPT1 was visualized in infant tissue using immunohistochemical staining. Other transporters [multidrug resistance protein 1 (MDR1), multidrug resistance-like protein 2 (MRP2), and organic anion transporter polypeptide 2B1 (OATP2B1)] were also stained to describe the localization in relation to PEPT1. Twenty-six intestinal samples (n = 20 neonates/infants, n = 2 pediatric, n = 4 adolescents) were analyzed. The young infant samples were collected at a median (range) gestational age at birth of 29.2 weeks (24.7-40) and postnatal age of 2.4 weeks (0-16.6). The PEPT1 mRNA expression of the neonates/infants was only marginally lower (0.8-fold) than the older children (P < 0.05). Similar and clear apical PEPT1 and MRP2 staining, apical and lateral MDR1 staining, and intraepithelial OATP2B1 staining at the basolateral membrane of the enterocyte were detected in 12 infant and 2 adolescent samples. Although small intestinal PEPT1 expression tended to be lower in neonates than in older children, this difference is small and tissue distribution is similar. This finding suggests similar oral absorption of PEPT1 substrates across the pediatric age range.
肠道寡肽转运体肽转运体1（PEPT1）（溶质载体家族15成员1，SLC15A1）以转运营养源二肽和三肽而最为人所知。其在药物吸收中的作用也日益受到认可。为了更好地了解PEPT1底物药物在幼儿中的处置情况，我们研究了整个儿童年龄范围内肠道PEPT1 mRNA的表达及组织定位。采用实时逆转录聚合酶链反应，对手术采集（新生儿和婴儿）或活检（大龄儿童和青少年）的小肠组织中的PEPT1 mRNA表达进行测定。比较了新生儿/婴儿与大龄儿童/青少年之间相对于绒毛蛋白mRNA表达的PEPT1 mRNA情况。采用免疫组织化学染色法观察婴儿组织中的PEPT1。还对其他转运体[多药耐药蛋白1（MDR1）、多药耐药相关蛋白2（MRP2）和有机阴离子转运多肽2B1（OATP2B1）]进行染色，以描述其与PEPT1相关的定位情况。分析了26份肠道样本（20例新生儿/婴儿、2例儿童、4例青少年）。幼儿样本采集时的出生胎龄中位数（范围）为29.2周（24.7 - 40周），出生后年龄为2.4周（0 - 16.6周）。新生儿/婴儿的PEPT1 mRNA表达仅略低于大龄儿童（0.8倍）（P < 0.05）。在12份婴儿样本和2份青少年样本中，检测到相似且明显的顶端PEPT1和MRP2染色、顶端和侧面的MDR1染色以及肠上皮细胞基底外侧膜处的上皮内OATP2B1染色。虽然新生儿小肠PEPT1表达往往低于大龄儿童，但这种差异较小且组织分布相似。这一发现表明，在整个儿童年龄范围内，PEPT1底物的口服吸收情况相似。
