title: Oxytocin evokes a pulsatile PGE2 release from ileum mucosa and is required for repair of intestinal epithelium after injury.
abstract: 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.
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Junhan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Haoyi
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: An
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Su
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005071:Evoked Potentials / Q000187:drug effects; D005472:Fluorouracil / Q000633:toxicity; D007082:Ileum / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007410:Intestinal Diseases / Q000139:chemically induced / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010121:Oxytocin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007477:Ions; D018045:Receptors, Oxytocin; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D010121:Oxytocin; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002118:Calcium; D005472:Fluorouracil; D007213:Indomethacin