Segment-specific effects of resveratrol on porcine small intestinal dipeptide absorption depend on the mucosal pH and are due to different mechanisms: potential roles of different transport proteins and protein kinases

Numerous beneficial features of the polyphenol resveratrol (RSV) have been demonstrated in several tissues and cell culture models. There is also evidence, that RSV impairs intestinal nutrient transport but the underlying mechanisms are not understood. The aim of the present study was to evaluate whether RSV has also an impact on the H+-coupled transport of peptides via the peptide transporter 1 (PepT1) and to characterize RSV mediated changes in the apical abundance of nutrients transport proteins and protein kinases that may be involved. RSV decreased the H+-coupled transport of peptides in the porcine small intestines in a pH and location specific manner (jejunum vs ileum) as measured in Ussing chamber experiments. The comparison of the effects of RSV with the effects of the cAMP/PKA-activating agent forskolin indicates that different mechanisms may be responsible in the intestinal segments. Additionally, it seems that the transport of peptides and glucose in the jejunum are inhibited via the same mechanism while there might be two mechanisms involved in the ileum. Functional data and protein expression data indicate, that, besides PepT1, the activity of the Na+/H+-exchanger 3 (NHE3) may be involved. Protein kinase A (PKA) and AMP-activated kinase (AMPK) are both activated by RSV while the extracellular regulated kinase (ERK) and the serum and glucocorticoid induced kinase (SGK) are widely unaffected. Although PKA and AMPK are activated, AMPK seems not to be related to the effects of RSV. Additionally, both the functional data and the protein expression data reveal some interesting pH- and segment-specific differences.