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Prosurvival and antiapoptotic effects of PGE 2 in radiation injury are mediated by EP 2 receptor in intestine

2003; American Physiological Society; Volume: 284; Issue: 3 Linguagem: Inglês

10.1152/ajpgi.00240.2002

1522-1547

Courtney W. Houchen, Mark Sturmoski, Shrikant Anant, Richard Breyer, William F. Stenson,

Inflammatory mediators and NSAID effects

The biological activities of PGE 2 are mediated through EP receptors (EP 1 –EP 4 ), plasma membrane G protein-coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP 2 receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP 2 null mice. EP 2 was expressed throughout the gut. Intestinal EP 2 mRNA increased fivefold after γ-irradiation. Crypt survival was diminished in EP 2 −/− mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP 2 −/− mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP 2 −/− mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP 2 receptor is expressed in mouse gastrointestinal epithelial cells and is upregulated following radiation injury. The effects of PGE 2 on both crypt epithelial apoptosis and intestinal crypt stem cell survival are mediated through the EP 2 receptor.