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Developmental expression of PEPT1 and PEPT2 in rat small intestine, colon, and kidney
H Shen1, D E Smith, F C Brosius
1College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
Insights
Mammalian peptide transporters (PEPT1 and PEPT2) show dynamic developmental expression in rat intestines and kidneys. Intestinal PEPT1 levels peak shortly after birth and at weaning, suggesting regulation by feeding.
Area of Science:
- Pharmacology and Physiology
- Developmental Biology
- Molecular Biology
Background:
- Mammalian peptide transporters (PEPT1 and PEPT2) are crucial for peptide absorption and drug delivery.
- Limited data exists on the developmental regulation of these transporters, particularly in young mammals.
Purpose of the Study:
- To investigate the developmental expression patterns of intestinal and renal oligopeptide transporters (PEPT1 and PEPT2) in rats from embryonic to adult stages.
- To analyze mRNA and protein levels in various intestinal segments (duodenum, jejunum, ileum, colon) and the kidney.
Main Methods:
- Quantitative analysis of PEPT1 and PEPT2 mRNA and protein expression.
- Tissue collection from rat intestines and kidneys at different developmental time points (fetal, neonatal, juvenile, adult).
Main Results:
- Intestinal PEPT1 expression peaked 3-5 days postpartum and showed a transient increase at day 24, coinciding with weaning.
- Adult intestinal PEPT1 protein levels were approximately 70% of the early postnatal peak.
- Colon exhibited significant PEPT1 expression in the first week of life, diminishing in adulthood.
- Renal PEPT1 and PEPT2 expression was less regulated and more pronounced in older rats.
- Peptide transporters were detected as early as day 20 of fetal development.
Conclusions:
- Intestinal PEPT1 expression is significantly influenced by the postpartum period and weaning, suggesting regulation by dietary factors like suckling.
- The colon may play a role in peptide transport during early life.
- Kidney transporters (PEPT1 and PEPT2) show a different developmental regulation pattern compared to the intestine.
Abstract:
Mammalian peptide transporters (PEPT1 and PEPT2) play a pivotal role in the absorption of small peptides from the intestine and kidney, respectively, and in the disposition and targeting of peptide or mimetic drugs. However, there are few reports on the molecular basis of their regulation, especially in the young. The aim of this study was to determine the developmental expression of intestinal and renal oligopeptide transporters in rats from embryonic to adult ages. Intestinal segments were collected (i.e. duodenum, jejunum, ileum, and colon) along with whole kidney, and their mRNA and protein levels were measured. Expression levels of PEPT1 were maximal 3-5 d after birth in the duodenum, jejunum, and ileum, and then declined rapidly. Expression was increased transiently at d 24, most notably in the ileum. Adult protein levels were approximately 70% of that observed on d 3-5. Significant PEPT1 expression was observed in colon during the first week of life, but levels were undetectable shortly thereafter through adulthood. PEPT1 and PEPT2 expression is less regulated in rat kidney and more pronounced in older animals. Peptide transporters were also present as early as d 20 of fetal life for all tissues tested. These results are unique in providing the developmental expression of peptide transporter mRNA and protein in distinct regions of the small intestine, colon, and kidney in rat. Our findings suggest that intestinal expression of PEPT1 is induced postpartum, possibly by suckling, and again at the time of weaning, and that the colon may participate in peptide transport early in life.