oxytocin and Intestinal-Diseases

We measured the short-circuit current (Isc) in rat ileum mucosa to identify the effect of oxytocin (OT) on mucosal secretion in small intestine. We identified a COX-2-derived pulsatile PGE2 release triggered by OT in rat ileum mucosa. OT receptors (OTR) are expressed in intestine crypt epithelial cells. Notably, OT evoked a dynamic change of [Ca(2+)]i in ileum crypts, which was responsible for this pulsatile release of PGE2. OT ameliorated 5-FU-, radiation- or DSS- induced injury in vivo, including the improvement of weight loss, reduced villus height and impaired survival of crypt transit-amplifying cells as well as crypt. Moreover, these protective effects of OT against intestinal injury were eliminated by coadministration of a selective inhibitor of PGE2, AH6809. Our findings strongly suggest that OT, a novel and important regulator of intestine mucosa barrier, is required for repair of intestinal epithelium after injury. Considering that OT is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent chemo-radiotherapy induced intestine injury or to treat IBD.

Topics: Animals; Antineoplastic Agents; Calcium; Cyclooxygenase 2; Dextran Sulfate; Dinoprostone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Evoked Potentials; Fluorouracil; Ileum; Immunohistochemistry; Indomethacin; Intestinal Diseases; Intestinal Mucosa; Ions; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Neoplasms; Oxytocin; Rats; Rats, Wistar; Receptors, Oxytocin; Wound Healing; Xanthones