Minimum biological domain of xenin-25 required to induce anion secretion in the rat ileum

•Xenin-25 has a variety of physiological functions in the gastrointestinal tract.•The details of the biological domain that induce ion transport of xenin-25 remain poorly understood.•The minimum biological domain of xenin-25 to induce anion secretion in the ileum contains the C-terminal peptapeptide.•Arg at position 21 is important to retain the biological activity of xenin-25 to induce anion secretion in the rat ileum. Xenin-25 has a variety of physiological functions in the gastrointestinal tract, including ion transport and motility. Xenin-25 and neurotensin show sequence homology, especially near their C-terminal regions. The sequence similarity between xenin-25 and neurotensin indicates that the effects of xenin-25 is mediated by the neurotensin receptor but some biological actions of xenin-25 are independent. We have previously reported that xenin-25 modulates intestinal ion transport and colonic smooth muscle activity. However, minimal biological domain of xenin-25 to induce ion transport was not clear. To improve the mechanistic understanding of xenin-25 and to gain additional insights into the functions of xenin-25, the present study was designed to determine the minimal biological domain of xenin-25 required for ion transport in the rat ileum using various truncated xenin fragments and analogues in an Ussing chamber system. The present results demonstrate that the minimum biological domain of xenin-25 to induce Cl−/HCO3− secretion in the ileum contains the C-terminal pentapeptide. Furthermore, Arg at position 21 is important to retain the biological activity of xenin-25 and induces Cl−/HCO3− secretion in the rat ileum.