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Am J Physiol Gastrointest Liver Physiol 284: G490-G498, 2003. First published November 13, 2002; doi:10.1152/ajpgi.00240.2002
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Vol. 284, Issue 3, G490-G498, March 2003

Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine

Courtney W. Houchen1, Mark A. Sturmoski1, Shrikant Anant1, Richard M. Breyer2, and William F. Stenson1

1 Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110; and 2 Department of Medicine, Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2372

The biological activities of PGE2 are mediated through EP receptors (EP1-EP4), plasma membrane G protein-coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP2 receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP2 null mice. EP2 was expressed throughout the gut. Intestinal EP2 mRNA increased fivefold after gamma -irradiation. Crypt survival was diminished in EP2-/- mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP2-/- mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP2 -/- mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP2 receptor is expressed in mouse gastrointestinal epithelial cells and is upregulated following radiation injury. The effects of PGE2 on both crypt epithelial apoptosis and intestinal crypt stem cell survival are mediated through the EP2 receptor.

prostaglandin; cyclooxygenase; prostaglandins; receptor signaling


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