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 post-treatment time for diarrhea onset was approximately 7 min, at a PGE2 dose of 200 micrograms/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 decrease 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 micrograms/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 micrograms/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
Rivière
P J
PJ
Department of Pharmacology, College of Medicine, University of Arizona, Tucson.
Farmer
S C
SC
Burks
T F
TF
Porreca
F
F
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced*; D015232:Dinoprostone / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D008026:Ligation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D015232:Dinoprostone