Moriarty K J, Higgs N B, Woodford M, Warhurst G, Turnberg L A
Department of Medicine, Hope Hospital (University of Manchester School of Medicine), Salford.
Gut. 1987 Jul;28(7):844-8. doi: 10.1136/gut.28.7.844.
Cisapride is a synthetic drug which binds, in vitro, to type 2 serotonin receptors. We examined the influence of serotonin and cisapride on ion transport across intestinal mucosa in vitro and studied the effect of cisapride on the response to serotonin. Segments of ileum of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. The addition of serotonin (10(-8) to 10(-4) M) to the serosal aspect of the mucosa caused a rapid, dose-dependent rise in short circuit current and transmural potential difference. Cisapride alone (5 X 10(-5) M), when added to the mucosal and serosal surfaces, had no effect on the short circuit current, transmural potential difference, resistance, or sodium and chloride fluxes across the mucosa. It did, however, inhibit the response of the mucosa to serotonin (10(-5) M) in a dose dependent manner and blocked it completely at a concentration of 5 X 10(-5) M. Serotonin (5 X 10(-5) M) increased serosal to mucosal flux of chloride from 12.6 +/- 0.8 to 15.2 +/- 0.6 mumol/cm2/h (p less than 0.025), thus reducing net chloride absorption from 4.65 +/- 0.81 to 1.49 +/- 1.04 mumol/cm2/h (p less than 0.05). This effect was completely blocked by cisapride (5 X 10(-5) M). In summary, cisapride inhibits the effect of serotonin on rat ileal ion transport, probably by blocking type 2 serotonin receptors.
西沙必利是一种合成药物，在体外可与2型5-羟色胺受体结合。我们在体外研究了5-羟色胺和西沙必利对肠道黏膜离子转运的影响，并探讨了西沙必利对5-羟色胺反应的作用。将雄性斯普拉格-道利大鼠的回肠段剥去肌层，安装在通量室中。向黏膜浆膜侧加入5-羟色胺（10^(-8)至10^(-4)M）可使短路电流和跨膜电位差迅速、剂量依赖性升高。单独加入西沙必利（5×10^(-5)M）至黏膜和浆膜表面时，对短路电流、跨膜电位差、电阻或黏膜钠和氯通量无影响。然而，它确实以剂量依赖性方式抑制黏膜对5-羟色胺（10^(-5)M）的反应，并在浓度为5×10^(-5)M时完全阻断。5-羟色胺（5×10^(-5)M）使氯从浆膜向黏膜的通量从12.6±0.8增加至15.2±0.6μmol/cm²/h（p＜0.025），从而使氯的净吸收从4.65±0.81减少至1.49±1.04μmol/cm²/h（p＜0.05）。这种作用被西沙必利（5×10^(-5)M）完全阻断。总之，西沙必利可能通过阻断2型5-羟色胺受体来抑制5-羟色胺对大鼠回肠离子转运的作用。
