Yokoyama T, Takasaki K, Kitazawa T, Karasawa A, Kusaka H
Drug Discovery Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sunto-gun, Shizuoka, Japan. stimulating action in the recovered period but not in the post-operative period. The mechanisms of t.
Life Sci. 2000 Sep 29;67(19):2281-92. doi: 10.1016/s0024-3205(00)00818-3.
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.
我们之前报道过，胃动素类似物KW-5139在清醒犬的术后及恢复阶段均能引起胃肠运动刺激作用。在本报告中，我们使用在胃窦、十二指肠、空肠、回肠和结肠植入力传感器的比格犬，比较了KW-5139在术后阶段与恢复阶段引起收缩的机制。此外，我们还研究了两个阶段中前列腺素F2α引起收缩的机制。KW-5139（0.5微克/千克，静脉注射）引起的胃收缩在恢复阶段被5-HT3受体拮抗剂昂丹司琼（0.1毫克/千克，静脉注射）预处理所抑制，但在术后阶段即使使用更高剂量的昂丹司琼（0.3 - 1毫克/千克，静脉注射）也不受影响。KW-5139在小肠和大肠引起的收缩在两个阶段均未被昂丹司琼抑制。KW-5139（0.5微克/千克，静脉注射）在胃窦、十二指肠、空肠和结肠引起的收缩在恢复阶段被毒蕈碱受体拮抗剂阿托品（0.05毫克/千克，静脉注射）预处理显著抑制，与术后阶段的抑制程度相同。前列腺素F2α（50微克/千克，静脉注射）在任何记录部位引起的收缩在恢复阶段未被昂丹司琼（0.1毫克/千克，静脉注射）预处理所影响。另一方面，阿托品（0.05毫克/千克，静脉注射）倾向于抑制胃和结肠的收缩。昂丹司琼和阿托品对前列腺素F2α引起收缩的这些作用在术后和恢复阶段没有差异。目前的结果表明，5-HT3受体参与KW-5139在恢复阶段而非术后阶段的运动刺激作用。讨论了这种变化的机制。
