Change of the involvement of 5-HT3 receptor in the gastric motor stimulating actions of KW-5139 (Leu13-motilin acetate) in the recovered and post-operative periods in dogs.

We have previously reported that KW-5139, a motilin analogue, evokes gastrointestinal motor stimulating action in the post-operative period as well as in the recovered period of conscious dogs. In this report, we compared the mechanisms of the KW-5139-induced contractions in the post-operative period with those in the recovered period using beagle dogs implanted force transducers in the gastric antrum, duodenum, jejunum, ileum and colon. In addition, we also examined the mechanisms of the prostaglandin F2alpha-induced contractions in both periods. The gastric contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) were inhibited by the pretreatment of ondansetron (0.1 mg kg(-1), i.v.), a 5-HT3 receptor antagonist, in the recovered period, but were not affected in the post-operative period even by higher doses of ondansetron (0.3-1 mg kg(-1), i.v.). The KW-5139-induced contractions in the small and large intestine were not inhibited by ondansetron in the both periods. The contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) in the gastric antrum, duodenum, jejunum and colon were significantly inhibited by the pretreatment with atropine (0.05 mg kg(-1), i.v.), a muscarinic receptor antagonist, in the recovered period as same extent as in the post-operative period. The contractions evoked by prostaglandin F2alpha (50 microg kg(-1), i.v.) in the any recording sites were not affected by the pretreatment with ondansetron (0.1 mg kg(-1), i.v.) in the recovered period. On the other hand, atropine (0.05 mg kg(-1), i.v.) tended to inhibit the gastric and colonic contractions. These effects of ondansetron and atropine on the prostaglandin F2alpha-induced contractions were not different between in the post-operative and recovered periods. The present results indicate that 5-HT3 receptors are involved in the KW-5139-induced motor stimulating action in the recovered period but not in the post-operative period. The mechanisms of the alteration were discussed.