Ooe M, Asano K, Haga K, Setoguchi M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Nihon Yakurigaku Zasshi. 1993 May;101(5):299-307. doi: 10.1254/fpj.101.5_299.
We studied the effect of Y-25130 on the intestinal fluid secretion induced by 5-HT and cholera toxin in rats. 1) Net fluid secretion was increased dose-dependently by intramesenteric artery infusion of 5-HT (1-10 micrograms/min). 2) Y-25130 (0.01-1 mg/kg, i.v.) inhibited the net fluid secretion induced by 5-HT (3 micrograms/min). Granisetron and ondansetron also inhibited the net fluid secretion induced by 5-HT. 3) Methysergide did not inhibit the fluid secretion, and neither atropine nor tetrodotoxin inhibited it. 4) Cholera toxin (1-10 micrograms/2 ml into jejunal loops) caused profuse net fluid secretion. 5) Y-25130 (1 mg/kg, i.v.) inhibited the net fluid secretion induced by cholera toxin (3 micrograms/2 ml). Granisetron was inhibitory and ondansetron tended to inhibit the cholera toxin-induced secretion. These results suggest that 5-HT may increase the net fluid secretion through 5-HT3 receptors, and cholera toxin-induced fluid secretion may be at least partially mediated by 5-HT3 receptors. It is expected that Y-25130 may be useful for treating secretory diarrhea in humans.
我们研究了Y-25130对大鼠5-羟色胺（5-HT）和霍乱毒素诱导的肠液分泌的影响。1）通过肠系膜动脉内输注5-HT（1-10微克/分钟），净液体分泌呈剂量依赖性增加。2）Y-25130（0.01-1毫克/千克，静脉注射）抑制了由5-HT（3微克/分钟）诱导的净液体分泌。格拉司琼和昂丹司琼也抑制了由5-HT诱导的净液体分泌。3）麦角新碱不抑制液体分泌，阿托品和河豚毒素也不抑制。4）霍乱毒素（1-10微克/2毫升注入空肠肠袢）引起大量净液体分泌。5）Y-25130（1毫克/千克，静脉注射）抑制了由霍乱毒素（3微克/2毫升）诱导的净液体分泌。格拉司琼具有抑制作用，昂丹司琼倾向于抑制霍乱毒素诱导的分泌。这些结果表明，5-HT可能通过5-HT3受体增加净液体分泌，霍乱毒素诱导的液体分泌可能至少部分由5-HT3受体介导。预计Y-25130可能对治疗人类分泌性腹泻有用。
