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Involvement of platelet-activating factor (PAF) in endotoxin-induced intestinal motor disturbances in rats
L Pons1, M T Droy-Lefaix, P Braquet
1Department of Pharmacology-INRA, Toulouse, France.
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) 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.
Insights
Endotoxin disrupts intestinal motility by altering migrating myoelectric complexes (MMC). Platelet-activating factor (PAF) and prostaglandins play key roles in these endotoxin-induced motor alterations.
Area of Science:
- Gastroenterology
- Pharmacology
- Physiology
Background:
- Intestinal motility is regulated by complex mechanisms.
- The migrating myoelectric complex (MMC) is a key pattern of intestinal electrical activity.
- Endotoxin can significantly alter gastrointestinal function.
Purpose of the Study:
- To investigate the effects of endotoxin on intestinal myoelectrical activity in rats.
- To explore the role of platelet-activating factor (PAF) and prostaglandins in endotoxin-induced changes in gut motility.
- To identify potential therapeutic targets for endotoxin-related gastrointestinal dysfunction.
Main Methods:
- Conscious, fasted rats with chronic duodeno-jejunum electrodes were used.
- Intravenous endotoxin and intraperitoneal platelet-activating factor (PAF) were administered.
- Specific PAF antagonist (BN 52021) and prostaglandin E2 (PGE2) antagonist (SC 19220) were used to block specific pathways.
- Intestinal myoelectrical activity, specifically MMC intervals, was monitored and analyzed.
Main Results:
- Endotoxin significantly increased the interval between MMCs in a dose-dependent manner.
- PAF mimicked the effects of endotoxin on MMC intervals.
- Administration of BN 52021 partially abolished endotoxin-induced motor alterations and fully blocked PAF-induced changes.
- Indomethacin and SC 19220 significantly reduced the duration of MMC inhibition caused by endotoxin and PAF.
Conclusions:
- Endogenous PAF release is partly responsible for endotoxin-induced intestinal motor alterations.
- Prostaglandins are also involved in mediating these endotoxin and PAF effects.
- Targeting PAF and prostaglandin pathways may offer therapeutic strategies for endotoxin-induced gastrointestinal disturbances.