Opposite central and peripheral control by endogenous opioids of intestinal motility in fed rats

1. The effects of the inhibitors of endopeptidase EC 24.11, thiorphan and phosphoramidon administered i.c.v. (40 micrograms kg-1) i.p. (400 micrograms kg-1), or orally (400 micrograms kg-1), on intestinal motor activity in fed rats was compared to the effects of similar doses of the angiotensin converting enzyme inhibitor, captopril and the synthetic enkephalin analogue [D-Ala2 Met5] enkephalinamide (Dalamide). Drugs were administered alone or after pretreatment with naloxone or N-methyl levallorphan (300 micrograms kg-1, i.p.) given 10 min prior to gavage with a standard meal. 2. In control conditions, in the duodenum, the disruption of the migrating myoelectric complex (MMC) by gavage with a standard meal lasted between 105.6 and 119.1 min. This duration was significantly decreased by thiorphan (60.3 +/- 15.0 min), phosphoramidon (67.9 +/- 7.3 min), captopril (26.3 +/- 10.2 min) and Dalamide (42.4 +/- 9.6 min), administered i.c.v. 3. In contrast, after the i.p. administration of thiorphan, phosphoramidon and Dalamide the delay in the return of the MMC pattern was increased. Such an effect was also seen after the oral administration of phosphoramidon or Dalamide. Neither i.p. nor oral captopril administration altered the duration of postprandial pattern. 4. A prior treatment with naloxone i.p. (300 micrograms kg-1) that had no effect per se, antagonized the effect produced by i.c.v. administration of thiorphan, phosphoramidon or Dalamide, but failed to reverse the effect of captopril. In contrast, i.p. administration of N-methyl levallorphan (300pgkg-1) did not affect the response induced by central administration of thiorphan, phosphoramidon, captopril or Dalamide, but was able to prevent that of thiorphan, phosphoramidon or Dalamide when they were administered i.p. or orally. 5. These data strongly support the hypothesis of a dual control by endogenous opioids of intestinal motility in the rat: a central component that favours, and a peripheral control that delays the occurrence of the MMC profile in fed rats.