Administration of cisplatin and methotrexate significantly increased 5-hydroxytryptamine (5-HT) release from intestinal tissues isolated at 72 h after administration in rats. Daily administration with nafamostat mesilate, a potent serine protease inhibitor, significantly inhibited the release of 5-HT induced by methotrexate, but not by cisplatin, in a dose-dependent manner. When applied to isolated ileal tissues in vitro, nafamostat mesilate also significantly inhibited the release of 5-HT induced by methotrexate, but not by cisplatin, in a concentration-dependent manner. These results suggest that serine proteases are involved in the mechanism of the methotrexate-induced release of 5-HT from the rat small intestine.

在大鼠给药后 72 小时，顺铂和甲氨蝶呤的给药显着增加了肠道组织中 5-羟色胺 (5-HT) 的释放。每天服用甲磺酸萘莫司他（一种有效的丝氨酸蛋白酶抑制剂）以剂量依赖性方式显着抑制甲氨蝶呤诱导的 5-HT 释放，但不能抑制顺铂诱导的 5-HT 释放。当应用于体外分离的回肠组织时，甲磺酸萘莫司他也以浓度依赖性方式显着抑制甲氨蝶呤诱导的 5-HT 释放，但不抑制顺铂诱导的 5-HT 释放。这些结果表明丝氨酸蛋白酶参与了甲氨蝶呤诱导的大鼠小肠释放 5-HT 的机制。