Cho C H, Koo M W, Ko J K
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Pharmacology. 1994 Sep;49(3):137-43. doi: 10.1159/000139227.
The involvement of 5-hydroxytryptamine (5-HT) in gastric function and mucosal damage has been defined. 5-HT also potentiates lesion formation in animals. The current study investigated further whether these actions are mediated through 5-HT3 receptors in rats. Ondansetron, a 5-HT3 receptor antagonist, was given subcutaneously, 2 or 4 mg/kg, 30 min before the gastric parameters were measured. The higher dose of ondansetron, 4 mg/kg, significantly increased gastric mucosal blood flow (GMBF) and also basal acid and Na+ secretion. However, it did not affect pepsin output. 5-HT time dependently reduced GMBF and pepsin secretion, but not that of acid and Na+. These actions were not altered by ondansetron pretreatment. The drug, however, dose dependently reduced ethanol-induced gastric mucosal lesions in the 5-HT-treated animals. These findings indicate that 5-HT3 receptors regulate not only basal GMBF, but also acid and Na+ secretion in stomachs. However, the depressive action of 5-HT on GMBF and pepsin secretion is most likely not mediated through 5-HT3 receptors. Ondansetron also modulates the toxicities of ethanol in the stomach and this action is likely to be mediated through the preservation of GMBF.
5-羟色胺（5-HT）在胃功能及黏膜损伤中的作用已得到明确。5-HT还可增强动物的损伤形成。本研究进一步探究了这些作用是否通过大鼠体内的5-HT3受体介导。在测量胃参数前30分钟，皮下注射5-HT3受体拮抗剂昂丹司琼，剂量为2或4毫克/千克。较高剂量的昂丹司琼（4毫克/千克）显著增加了胃黏膜血流量（GMBF）以及基础胃酸和钠离子分泌。然而，它并未影响胃蛋白酶的分泌量。5-HT可使GMBF和胃蛋白酶分泌呈时间依赖性减少，但对胃酸和钠离子分泌无此作用。昂丹司琼预处理并未改变这些作用。然而，该药物在5-HT处理的动物中可剂量依赖性地减少乙醇诱导的胃黏膜损伤。这些发现表明，5-HT3受体不仅调节基础GMBF，还调节胃中的胃酸和钠离子分泌。然而，5-HT对GMBF和胃蛋白酶分泌的抑制作用很可能不是通过5-HT3受体介导的。昂丹司琼还可调节乙醇对胃的毒性，且此作用可能是通过维持GMBF介导的。
