Background/Aims

We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice.

Methods

Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT₃ receptor agonist), apomorphine, lorglumide (CCK₁ receptor antagonist), ondansetron, and haloperidol alone and in combination.

Results

IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8.

Conclusions

These results suggest that CCK-CCK₁ receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.

Graphical Abstract

中文翻译：

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胆囊收缩素诱导的十二指肠胃胆汁反流会增加重新喂养小鼠中吲哚美辛诱导的胃窦溃疡的严重程度

背景/目标

我们检查了胆囊收缩素 (CCK) 在阿托品或多巴胺引起的小鼠胃轻瘫引起的吲哚美辛 (IND) 诱发的胃窦溃疡恶化中的作用。

方法

雄性小鼠禁食 22 小时后喂养 2 小时（重新喂养）。重新喂食后给予吲哚美辛（IND；10 mg/kg，皮下注射）；IND治疗后24小时检查胃部病变。在另一项实验中，小鼠在禁食 22 小时后喂食 2 小时，然后在喂食期结束 1.5 小时后取出胃。_{在使用或不使用促动力药物和抗动力药物CCK-八肽（CCK-8）、阿托品、多巴胺、SR57227（5-HT 3}受体）的情况下，测量胃窦病变、胃内容物量和胃腔胆汁酸浓度。激动剂）、阿扑吗啡、洛格米特（CCK ₁受体拮抗剂）、昂丹司琼和氟哌啶醇单独或组合。

结果

IND 仅在重新喂养的小鼠胃窦中产生严重损伤。重新喂食后立即施用 CCK-8、阿托品、多巴胺、SR57227 和阿扑吗啡会增加胆汁反流并加重 IND 引起的胃窦病变。通过洛格鲁胺预处理可以显着防止这些影响。尽管阿托品和多巴胺也会增加胃内容物的量，但洛格鲁米特对阿托品和多巴胺引起的胃排空延迟没有影响。昂丹司琼和氟哌啶醇分别显着抑制阿托品和多巴胺引起的胆汁反流增加和胃窦病变加重，但不影响CCK-8的作用。

结论

这些结果表明，CCK-CCK ₁受体信号在阿托品和多巴胺诱导的胃轻瘫期间增加胆汁反流，加剧 IND 诱导的胃窦溃疡。

图形概要