Role of Vagal Innervation in Diurnal Rhythm of Intestinal Peptide Transporter 1 (PEPT1)

Abstract

BackgroundProtein is absorbed predominantly as di/tripeptides via H+/peptide cotransporter-1 (PEPT1). We demonstrated previously diurnal variations in expression and function of duodenal and jejunal but not ileal PEPT1; neural regulation of this pattern is unexplored. HypothesisComplete abdominal vagotomy abolishes diurnal variations in gene expression and transport function of PEPT1. MethodsTwenty-four rats maintained in a 12-h light/dark room [6AM–6PM] underwent abdominal vagotomy; 24 other rats were controls. Four weeks later, mucosal levels of mRNA and protein were measured at 9AM, 3PM, 9PM, and 3AM (n = 6 each) by quantitative real-time PCR and Western blots, respectively; transporter-mediated uptake of dipeptide (Gly–Sar) was measured by the everted-sleeve technique. ResultsDiurnal variation in mRNA, as in controls, was retained post-vagotomy in duodenum and jejunum (peak at 3PM, p < 0.05) but not in ileum. Diurnal variations in expression of protein and Gly–Sar uptake, however, were absent post-vagotomy (p > 0.3). Similar to controls, maximal uptake was in jejunum after vagotomy (Vmax, nmol/cm/min: jejunum vs. duodenum and ileum; 163 vs. 88 and 71 at 3AM; p < 0.04); Km remained unchanged. ConclusionsVagal innervation appears to mediate in part diurnal variations in protein expression and transport function of PEPT1, but not diurnal variation in mRNA expression of PEPT1.