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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / toxicity
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Calcium / metabolism
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / metabolism
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Dextran Sulfate / toxicity
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Dinoprostone / analysis
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Dinoprostone / antagonists & inhibitors
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Dinoprostone / metabolism*
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay
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Evoked Potentials / drug effects
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Fluorouracil / toxicity
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Ileum / drug effects
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Ileum / injuries
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Ileum / metabolism
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Immunohistochemistry
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Indomethacin / pharmacology
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Intestinal Diseases / chemically induced
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Intestinal Diseases / drug therapy
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Intestinal Mucosa / drug effects*
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Intestinal Mucosa / injuries
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Intestinal Mucosa / metabolism
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Ions / chemistry
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Ions / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Microscopy, Fluorescence
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Neoplasms / drug therapy
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Neoplasms / radiotherapy
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Oxytocin / pharmacology*
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Oxytocin / therapeutic use
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Rats
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Rats, Wistar
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Receptors, Oxytocin / metabolism
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Wound Healing / drug effects
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Xanthones / pharmacology
Substances
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Antineoplastic Agents
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Ions
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Receptors, Oxytocin
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Xanthones
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6-isopropoxy-9-oxoxanthene-2-carboxylic acid
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Oxytocin
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Dextran Sulfate
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Cyclooxygenase 2
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Dinoprostone
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Calcium
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Fluorouracil
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Indomethacin