EFFECT OF A SELECTIVE 5-HT3 RECEPTOR AGONIST ON GASTRIC-MOTILITY IN FASTED AND FED DOGS

The effect of m-chlorophenylbiguanide, a selective 5-HT3 receptor agon ist, on gastric antral motility was investigated in conscious dogs wit h a force transducer implanted chronically. m-Chlorophenylbiguanide (0 .1-1 mg/kg i.v.) dose dependently enhanced antral motility in the fast ed state, and the amplitude of m-chlorophenylbiguanide (1 mg/kg i.v.)- induced antral contractions reached the level of natural phase III con tractions. In contrast, m-chlorophenylbiguanide reduced the amplitude of antral contractions in the fed state. A selective 5-HT3 receptor an tagonist, ramosetron (0.0003-0.03 mg/kg i.v.), inhibited both effects of m-chlorophenylbiguanide. m-Chlorophenylbiguanide (1 mg/kg i.v.)-ind uced contractions were inhibited by atropine (0.03 or 0.1 mg/kg i.v.). These results indicate that pharmacological activation of 5-HT3 recep tors has opposite effects on canine gastric antral motility in the fas ted and in the fed state, being stimulatory and inhibitory, respective ly. The stimulatory effect seems to be mediated mainly via the release of acetylcholine.