title: Human Intestinal PEPT1 Transporter Expression and Localization in Preterm and Term Infants.
abstract: 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.
authors.affiliation: 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.).
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mooij
authors.affiliation: 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.).
authors.forename: Barbara E A
authors.initials: BE
authors.lastname: de Koning
authors.affiliation: 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.).
authors.forename: Dicky J
authors.initials: DJ
authors.lastname: Lindenbergh-Kortleve
authors.affiliation: 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.).
authors.forename: Ytje
authors.initials: Y
authors.lastname: Simons-Oosterhuis
authors.affiliation: 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.).
authors.forename: Bianca D
authors.initials: BD
authors.lastname: van Groen
authors.affiliation: 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.).
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: 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.).
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.affiliation: 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.) s.dewildt@erasmusmc.nl.
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D000074011:Peptide Transporter 1 / Q000235:genetics / Q000378:metabolism*; D047928:Premature Birth; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047929:Term Birth
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C082186:SLC15A1 protein, human; C450859:SLCO2B1 protein, human