Assessment of the role of platelet-activating factor in an animal model of inflammatory bowel disease.
Using a rat model of chronic colitis, the role of PAF-acether as a mediator of intestinal inflammation was assessed. Rats were treated with a specific PAF-acether antagonist, BN52021, during the first 4 days after induction of colitis, or during the period of 4-7 days after induction of colitis. The effects of treatment with BN52021 were compared to those of treatment with 5-aminosalicylic acid. BN52021 and 5-aminosalicyclic acid were without significant effect on colonic damage score when administered intracolonically on days 1-4 after induction of colitis. However, when given on days 4-7 after induction of colitis, both drugs significantly accelerated the healing of ulcers and reduced the incidence of adhesions and diarrhea. Intraperitoneal administration of BN52021 also resulted in a significant reduction of colonic damage scores, while administration of 5-aminosalicyclic acid via this route was without significant effect. Using an in vitro superfusion system, the effects of PAF-acether on contractility of segments of ascending colon were assessed. Tissue segments from normal rats contracted to doses of PAF-acether as low as 0.5 pg. However, non-inflamed segments of ascending colon from rats in which colitis was induced 2 weeks earlier were relatively insensitive to PAF-acether. The results of the present study demonstrate that PAF-acether is unlikely to play an important role in the acute inflammatory response in this model, but may be important in the prolongation of inflammation and ulceration in this model. The studies on contractility of ascending colon suggest that changes in tissue sensitivity to PAF-acether may occur as a consequence of inflammation.
Wallace
J L
JL
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Braquet
P
P
Ibbotson
G C
GC
MacNaughton
W K
WK
Cirino
G
G
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004224:Diterpenes; D046934:Ginkgolides; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008297:Male; D019804:Mesalamine; D009119:Muscle Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014302:Trinitrobenzenesulfonic Acid
D000636:Aminosalicylic Acids; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; C045856:ginkgolide B