Involvement of platelet-activating factor (PAF) in endotoxin-induced intestinal motor disturbances in rats.
Intestinal myoelectrical activity was investigated in conscious fasted rats chronically implanted with Nichrome electrodes in the duodeno-jejunum. Motility of the small intestine was characterized by the presence of migrating myoelectric complex (MMC) occurring regularly at 16.2 +/- 5.8 minute intervals. Intravenous administration of endotoxin (E. coli S.0111:B4) at a dose of 50 micrograms/kg increased the interval between MMC to 112.6 +/- 26.8 min, the duration of these effects being dose-related between 10 to 100 micrograms/kg. Such a typical myoelectrical alteration, corresponding to rapidly propagated groups of spike bursts, was mimicked by the IP administration of PAF at doses of 10 to 50 micrograms/kg. Previous administration of BN 52021, a specific PAF antagonist at a dose of 50 mg/kg abolished the motor alterations induced by IP injection of PAF (25 micrograms/kg) and significantly (p less than 0.01) reduced by 61.2% those induced by IV endotoxin (50 micrograms/kg). Indomethacin (10 mg/kg IP) as well as SC 19220 (5 mg/kg IV), a PGE2 antagonist, injected prior to endotoxin (50 micrograms/kg IV) or PAF (25 micrograms/kg IP) also reduced significantly (p less than 0.01) the duration of MMC inhibition. It is concluded that endogenous release of PAF is partly responsible for the intestinal motor alterations induced by endotoxin; these effects, strongly reduced after treatment with BN 52021, are also mediated through the release of prostaglandins.
Pons
L
L
Department of Pharmacology-INRA, Toulouse, France.
Droy-Lefaix
M T
MT
Braquet
P
P
Buéno
L
L
D000818:Animals; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D004224:Diterpenes; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D004576:Electromyography; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005769:Gastrointestinal Motility / Q000187:drug effects*; D046934:Ginkgolides; D007213:Indomethacin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D004224:Diterpenes; D004731:Endotoxins; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; C045856:ginkgolide B; D007213:Indomethacin