Orally administered kappa but not mu opiate agonists enhance gastric emptying of a solid canned food meal in dogs.
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.
Gué
M
M
Department of Pharmacology INRA, Toulouse, France, France.
Fioramonti
J
J
Junien
J L
JL
Bueno
L
L
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000821:Animal Feed; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D001575:Benzomorphans; D004232:Diuretics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001569:Benzodiazepines; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C035470:tifluadom