Change of the involvement of 5-HT3 receptor in the gastric motor stimulating actions of KW-5139 (Leu(13)-motilin acetate) in the recovered and post-operative periods in dogs

We have previously reported that KW-5139, a motilin analogue, evokes gastro intestinal 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 perio d with those in the recovered period using beagle dogs implanted force tran sducers in the gastric antrum, duodenum, jejunum, ileum and colon. In addit ion, we also examined the mechanisms of the prostaglandin F-2 alpha-induced contractions in both periods. The gastric contractions evoked by KW-5139 ( 0.5 mu g 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, b ut were not affected in the post-operative period even by higher doses of o ndansetron (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 pe riods. The contractions evoked by KW-5139 (0.5 mu g kg(-1), i.v,) in the ga stric antrum, duodenum, jejunum and colon were significantly inhibited by t he 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-operativ e period. The contractions evoked by prostaglandin F-2 alpha (50 mu g kg(-1 ), i.v.) in the any recording sites were not affected by the pretreatment w ith 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 co lonic contractions. These effects of ondansetron and atropine on the prosta glandin F-2 alpha-induced contractions were not different between in the po st-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 o f the alteration were discussed. (C) 2000 Elsevier Science Inc. All rights reserved.