Orally administered kappa but not mu opiate agonists enhance gastric emptying of a solid canned food meal in dogs.

Abstract

The effects of oral administration of selective mu (D-Ala2, N-Me-p-nitro-Phe4, Gly5-ol-DAGO, morphine) and/or kappa (3,4 dichloro-N-methyl N [2-(1. fyrrolidinyl) cyclohexyl]-benzene acetamide-U-50488, tifluadom) or mixed agonist (N-desmethyltrimebutine) opioid on gastric emptying have been evaluated using a radiolabelled [57Co] canned food meal in dogs fitted with gastric cannulas. In control conditions (placebo) the percentage of solids emptied 1 h after feeding was 27.3 +/- 4.1%. When given orally at doses of 0.01 to 0.5 mg kg-1, U-50488 increased significantly (P less than 0.05) by 29.1 to 60.8% in a dose-related manner (r-0.94, P less than 0.01) the amount of gastric emptying of the meal in 1 h. This effect was reproduced by oral administration of tifluadom (0.01 to 0.1 mg kg-1) and by N-desmethyltrimebutine (0.1 to 1 mg kg-1). In contrast, the gastric emptying was unaffected by DAGO and morphine at low doses (0.01 and 0.1 mg kg-1) but significantly (P less than 0.05) slowed with higher doses of morphine. The increases in amount of gastric emptying induced by tifluadom, U-50488 and N-desmethyltrimebutine were abolished by previous administration of naloxone (0.1 mg kg-1 i.v.) and [(3-furylmethyl) noretazocine]-MR 22-66 (0.1 mg kg-1 i.v.). These results indicate that orally administered kappa, but not mu agonists at doses not exceeding 1 mg kg-1 enhance the amount of gastric emptying of a solid meal in dogs and suggest that this is due to a selective local stimulation of kappa mucosal or submucosal opiate receptors at antroduodenal level.