Prostaglandin E₂-induced diarrhea in mice: Importance of colonic secretion

The present study has investigated the basis for induction of diarrhea by prostaglandin (PG)E₂ in mice. When given i.p., PGE₂ induced a dose- and time-dependent diarrhea; the shortest posttreatment time for diarrhea onset was approximately 7 min, at a PGE₂ dose of 200 μg/kg. At this dose, PGE₂ also produced accumulation of fluid in the small intestine and in the colon (enteropooling). The enteropooling reached its maximum by 9 min and did not decrese until approximately 11 min (i.e., 2 to 4 min after the mean time for diarrhea onset). PGE₂ treatment altered neither gastric emptying nor gastrointestinal propulsion, but strongly enhanced the expulsion of a glass bead from the colon (i.e., decreased the time to bead expulsion). The shortest time to expulsion of the glass bead was observed at 200 μg/kg i.p. The induction of diarrhea by PGE₂ was unaffected by cecectomy, or sham-cecectomy, but the dose-response curve for time to onset of diarrhea by i.p. PGE₂ was displaced to the right in animals with ligations of the ileo-ceco-colonic (ICC) junctions. The intraluminal fluid accumulation in the colon, evaluated in mice with ICC ligations, was increased by PGE₂ administration within 2 min and remained greater than in vehicle-treated animals until the onset of diarrhea. The stimulation of colonic bead expulsion produced by i.p. PGE₂ in control mice was not observed in animals with acute ICC ligations, even at i.p. doses up to 800 μg/kg. The presence of diarrhea in ICC-ligated animals, in spite of the inhibition of PGE₂-induced colonic propulsive effects in these animals, emphasizes the importance of fluid accumulation in the colon whereas the delay in diarrhea occurrence also demonstrates the additional importance of colonic propulsive activity in the prompt initiation of diarrhea. PGE₂-induced diarrhea in mice appears to be secondarily maintained by fluid accumulated in the small intestine, as seen by the decrease in small intestinal fluid levels at times substantially after the initiation of diarrhea.