The kappa agonist fedotozine modulates colonic distention-induced inhibition of gastric motility and emptying in dogs.
OBJECTIVE
Gastric motor disturbances, associated with a delay in gastric emptying, occur in patients with the irritable bowel syndrome. The influence of fedotozine and kappa agonists on the cologastric reflex produced by nonpainful colonic distention was evaluated in conscious dogs.


METHODS
Colonic distention was applied in dogs fitted with either strain gauges or gastric cannula to assess its influence on gastrointestinal motility and gastric emptying, respectively.


RESULTS
Colonic distention delayed the occurrence of gastric migrating motor complex by 141%, an effect blocked by intravenous fedotozine, U 50,488 (25 and 50 micrograms/kg), and hexamethonium (0.5 mg/kg) but not by D-Ala2, N-methyl, Phe4, Gly5-ol enkephalin (1, 5, and 10 micrograms/kg), granisetron (50 and 100 micrograms/kg), or bretylium tosylate (5 mg/kg). Nor-binaltorphimine hydrochloride (1 mg/kg intravenously) eliminated the suppressive action of fedotozine. Colonic distention reduced the 1-hour gastric emptying of solids by 40.1%, an effect blocked by fedotozine and U 50,488 (50 and 100 micrograms/kg); nor-binaltorphimine hydrochloride (1 mg/kg) antagonized the blocking effect of fedotozine.


CONCLUSIONS
Fedotozine acts through kappa receptors to block the colonic distention-induced delay on gastric motility and emptying. The cologastric reflex involves nicotinic ganglionic receptors but not adrenergic pathway and 5-hydroxytryptamine 3 receptors.
Gué
M
M
Institut de Recherche Jouveinal, Fresnes, France.
Junien
J L
JL
Buéno
L
L
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology*; D001949:Bretylium Compounds / Q000494:pharmacology; D002404:Catheterization; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D017829:Granisetron / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D012018:Reflex / Q000187:drug effects; D013270:Stomach / Q000187:drug effects* / Q000502:physiology
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001593:Benzyl Compounds; D001949:Bretylium Compounds; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins; D017829:Granisetron; D018738:Hexamethonium; D009271:Naltrexone; D009292:Narcotic Antagonists; D011437:Propylamines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; C067749:fedotozine; C055382:naltrindole; C045166:bretylium