Role of platelet-activating factor (PAF) and prostaglandins in colonic motor and secretory disturbances induced by Escherichia coli endotoxin in conscious rats.
The involvement of prostaglandins (PGs) and platelet-activating factor (PAF) in the effects of Escherichia coli endotoxin on colonic motility, transit time, and fecal dry matter (DM) in rats were evaluated in this study. Myoelectric activity was investigated in a first group of male Wistar rats chronically implanted with intraparietal nichrome electrodes in the proximal colon. A second group of animals was chronically fitted with an intracolonic catheter (+2 cm from the cecocolonic junction); colonic transit time was then calculated as the Mean Retention Time (MRT) of 51Cr chromate sodium (1 microCi 0.1ml) administered through the intracolonic catheter and determined in the faeces collected at 1 hour interval on a conveyor belt. Fecal DM was measured after 24h dessication at 103 degrees C. E. coli endotoxin (50 micrograms/kg ip) increased the frequency of colonic contractions and decreased both colonic MRT and fecal DM. PAF (25 micrograms/kg ip) also decreased colonic MRT and fecal DM, and increased the frequency of colonic contractions. BN 50730 (10 mg/kg ip), a specific PAF receptor antagonist, blocked the effects of PAF and reduced those of endotoxin on colonic motility and transit time, but did not affect either the endotoxin- or the PAF-induced fecal DM decrease. Indomethacin (10 mg/kg ip) and SC 19220 (5 mg/kg ip) reduced the increased frequency of colonic contractions induced by endotoxin and PAF, and antagonized their effects on MRT and fecal DM. These results indicate that 1) E. coli endotoxin increases both colonic motility and transit, and decreases fecal DM, 2) PAF displays similar effects, 3) the action of endotoxin on colonic motility and transit is partly mediated by PAF and PGs while its secretory effects only depend upon PGs generation.
Department of Pharmacology INRA, Toulouse, France.
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Droy-Lefaix
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Buéno
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005243:Feces; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D010972:Platelet Activating Factor; D011453:Prostaglandins; C044101:endotoxin, Escherichia coli