Ohtawa M, Mizumoto A, Hayashi N, Yanagida K, Itoh Z, Omura S
Gastrointestinal Laboratories, Gunma University, Maebashi, Japan.
Gastroenterology. 1993 May;104(5):1320-7. doi: 10.1016/0016-5085(93)90340-i.
The pharmacological properties of EM523, a nonpeptide motilin agonist, have not been well characterized.
The prokinetic effect of EM523 on motor-stimulating activity in the stomach, duodenum, and jejunum in seventeen conscious dogs was studied using force transducers implanted long term. EM523 (0.3-10.0 micrograms/kg) and receptor antagonists were injected intravenously during the interdigestive state.
EM523 induced phase III-like contractions in a dose-dependent manner, and the contractions were inhibited dose dependently by pretreatment with cholinergic and 5-HT3 receptor antagonists and dopamine but not by adrenoceptor and opiate antagonists or methysergide. The plasma immunoreactive motilin level was increased after EM523 to 60% of the mean maximum value during the spontaneous phase III contractions. Pretreatment with anti-canine motilin serum inhibited EM523-induced contractions by 19.2% in the motor index, but the contractile pattern was not affected.
EM-523-induced phase III-like contractions are brought about through the cholinergic neural pathway and 5-HT3 receptors, and endogenous motilin release is partially involved.
非肽类胃动素激动剂EM523的药理特性尚未得到充分表征。
使用长期植入的力传感器，研究了EM523对17只清醒犬胃、十二指肠和空肠运动刺激活性的促动力作用。在消化间期静脉注射EM523（0.3 - 10.0微克/千克）和受体拮抗剂。
EM523以剂量依赖性方式诱导III期样收缩，胆碱能和5 - HT3受体拮抗剂以及多巴胺预处理可剂量依赖性地抑制这些收缩，但肾上腺素能受体和阿片类拮抗剂或麦角新碱则不能。EM523给药后，血浆免疫反应性胃动素水平升高至自发III期收缩期间平均最大值的60%。用抗犬胃动素血清预处理可使EM523诱导的收缩在运动指数上降低19.2%，但收缩模式未受影响。
EM - 523诱导的III期样收缩是通过胆碱能神经通路和5 - HT3受体实现的，内源性胃动素释放部分参与其中。
