title: Influence of enkephalinase inhibitors on gastric emptying in mice depends on the nature of the meal.
abstract: The effects of two enkephalinase inhibitors (thiorphan and acétorphan) and DALAMIDE on gastric emptying of fat or non-fat meals were evaluated in mice. When administered intraperitonally at low doses (0.1 and 0.2 mg/kg) 30 min prior to a fatty (milk) meal, both thiorphan and acetorphan increased significantly (P less than 0.01) gastric emptying; these effects were maximal for 0.2 and 0.1 mg/kg respectively and decreased progressively to be not significant for doses higher than 5 mg/kg for thiorphan and 0.5 mg/kg for acetorphan. Similarly DALAMIDE given IP increased significantly (P less than 0.05) gastric emptying at doses of 0.5 and 1 mg/kg while a slowing of gastric emptying was obtained for 10 times higher doses. The effects of thiorphan (0.2 mg/kg) and DALAMIDE (0.5 mg/kg) were blocked by previous administration of naloxone (0.3 mg/kg) and methyl-naloxone (0.5 mg/kg) while only naloxone (0.3 mg/kg) blocked the slowing effect of high dose of DALAMIDE. Administered prior to a non-fat meal, thiorphan (1 mg/kg) stimulated gastric emptying and inhibited it at higher dosage (10 mg/kg). Neither acetorphan nor DALAMIDE at similar dosages affected the gastric emptying of a non-fat meal and the effects of thiorphan (1 and 0.1 mg/kg) were not blocked by naloxone (0.3 mg/kg). It is concluded that enkephalinase inhibitors (thiorphan and acetorphan) administered systemically stimulate the gastric emptying of a fat meal by increasing enkephalin levels in peripheral tissues, while thiorphan exhibits non-opiate effects on gastric emptying of a non-fat meal.
authors.affiliation: Department of Pharmacology INRA, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Liberge
authors.forename: P M
authors.initials: PM
authors.lastname: Rivière
authors.forename: L
authors.initials: L
authors.lastname: Buéno
mesh_terms: D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D051379:Mice; D015244:Thiorphan / Q000031:analogs & derivatives; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D000603:Amino Acids, Sulfur; D004041:Dietary Fats; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C049331:racecadotril; D015244:Thiorphan; D008625:Tiopronin