Involvement of platelet-activating factor (PAF) in endotoxin-induced intestinal motor disturbances in rats

Abstract

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) occuring regularly at 16.2 ± 5.8 minute intervals. Intravenous administration of endotoxin (E. coli S.O111:B4) at a dose of 50 μg/kg increased the interval between MMC to 112.6 ± 26.8 min, the duration of these effects being dose-related between 10 to 100 μg/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 μg/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 μg/kg) and significantly (p<0.01) reduced by 1.2% those induced by IV endotoxin (50 μg/kg). Indomethacin (10 mg/kg IP) as well as SC 19220 (5 mg/kg IV), a PGE 2 antagonist, injected prior to endotoxin (50μg/kg IV) or PAF (25 μg/kg IP) also reduced significantly (p<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.