Platelet-activating factor and interleukin 1 are involved in colonic dysmotility in experimental colitis in rats.
BACKGROUND
Intracolonic administration of trinitrobenzene sulfonic acid (TNBS) to rats produces chronic colitis associated with an increased release of eicosanoids, platelet-activating factor (PAF), and interleukins.


METHODS
Motor effects of TNBS on proximal colon were evaluated electromyographically in rats. Mediator involvement was investigated using eicosanoids and PAF antagonists.


RESULTS
The colonic myoelectrical activity was 59 +/- 17 spike bursts per hour lasting 6.9 +/- 1.3 seconds. Two to eight days after TNBS treatment, spike-burst duration was significantly (P < 0.05) higher, with a maximal 1.5-4-fold enhancement at day 3. These alterations were significantly (P < 0.05) reduced by daily treatment with MK-886, a 5-lipoxygenase inhibitor (10 mg/kg, orally), whereas indomethacin (1 mg/kg per day, intramuscularly) was ineffective. At day 3, RP55778, a PAF antagonist (45, 60 mg/kg, intraperitoneally), and rIRAP, an interleukin 1 antagonist (0.3 mg/kg, intraperitoneally) but not KT1-32, a thromboxane A2 antagonist (30, 60 mg/kg orally), nor SKF104,353, a leukotriene D4 antagonist (2, 4 mg/kg, orally), significantly (P < 0.05) reduced the TNB-induced motor effects.


CONCLUSIONS
TNBS-induced colitis in rats involves a delayed long-lasting dysmotility involving PAF, interleukin 1, and some leukotrienes but not leukotriene D4, thromboxane A2, or other cyclo-oxygenase products.
Morteau
O
O
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
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D000818:Animals; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects; D016859:Lipoxygenase Inhibitors; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007375:Interleukin-1; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D014302:Trinitrobenzenesulfonic Acid