Influence of enkephalinase inhibitors on gastric emptying in mice depends on the nature of the meal.
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.
Liberge
M
M
Department of Pharmacology INRA, Toulouse, France.
Rivière
P M
PM
Buéno
L
L
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*
D000603:Amino Acids, Sulfur; D004041:Dietary Fats; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C049331:racecadotril; D015244:Thiorphan; D008625:Tiopronin