Effects of 5-hydroxytryptamine 3 receptor antagonists on gastrointestinal motor activity in conscious dogs

We studied the effect of 5-hydroxytryptamine 3 (5-HT3) receptor antagonists on gastrointestinal (GI) motor activity in conscious dogs with force transducers implanted chronically. During the digestive state, GR38032F, BRL 43694 and ICS 205-930 did not affect GI motor activity at all at doses up to 1 mg/kg, whereas BRL 24924 at 1.0 mg/kg i.v. significantly stimulated GI motor activity from the stomach to the colon. When GR38032F, BRL 43694 or ICS 205-930 was given i.v. at doses of 0.1 to 1.0 mg/kg during the phase I period, no direct effect was observed on GI motor activity, but the treatment inhibited the occurrence of the subsequent phase III activity in the stomach completely and inhibited it partially in the duodenum without affecting the plasma motilin concentration. GR38032F, BRL 43694 and ICS 205-930 did not influence the caudal migration of phase III activity in the small intestine. In contrast, BRL 24924 at doses of 0.1 to 1.0 mg/kg i.v. significantly stimulated GI motor activity during the phase I period. On the other hand, when GR38032F, BRL 43694 or ICS 205-930 was given during natural or motilin-induced phase III activity, the total contractions in the stomach and partial contractions in the duodenum were inhibited but the caudal propagation of phase III activity in the small intestine was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)