Satoh M, Sakai T, Sano I, Fujikura K, Koyama H, Ohshima K, Itoh Z, Omura S
Gastrointestinal Research Laboratory, Gunma University, Maebashi, Japan.
J Pharmacol Exp Ther. 1994 Oct;271(1):574-9.
Erythromycin and its derivatives are known to induce phase III-like contractions, which are similar to those induced by motilin, in the human gastrointestinal tract during the interdigestive state, but few detailed in vitro studies have been reported. We evaluated EM574, an erythromycin derivative, as a motilin receptor agonist in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes, receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips in a concentration-dependent manner (10(-7)-10(-5) M), and this contractile effect was unaffected by pretreatment with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at 10(-7) M, which was comparable to the response to motilin. EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10(-9) M, compared with 4.5 x 10(-9) M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were localized in the muscle layers, and that the labeling disappeared in the presence of a 1000 times molar concentration of EM574. We conclude that EM574 directly stimulates smooth muscle cell contraction by acting on motilin receptors in the human gastric antrum in vitro.
已知红霉素及其衍生物在消化间期可诱导人胃肠道出现类似于胃动素诱导的Ⅲ期样收缩，但体外详细研究报道较少。我们采用肌条收缩研究、分离的心肌细胞研究、受体结合试验和组织切片放射自显影技术，在体外评估了一种红霉素衍生物EM574作为人胃窦部胃动素受体激动剂的作用。EM574以浓度依赖性方式（10^(-7)-10^(-5) M）刺激肌条收缩，且这种收缩效应不受阿托品或河豚毒素预处理的影响。分离的心肌细胞对EM574产生收缩反应，在10^(-7) M时缩短峰值与对胃动素的反应相当。EM574特异性置换与平滑肌匀浆结合的125I-胃动素，其解离常数（Kd）值为7.8×10^(-9) M，而胃动素的Kd值为4.5×10^(-9) M。放射自显影片显示，125I-胃动素结合位点定位于肌层，且在1000倍摩尔浓度的EM574存在时标记消失。我们得出结论，EM574在体外通过作用于人胃窦部的胃动素受体直接刺激平滑肌细胞收缩。
