Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

Autor: Satoh H; Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395, Japan. h_satoh@gaia.eonet.ne.jp., Akiba Y; Greater Los Angeles Veterans Affairs Healthcare System, B114, R217, West LA VAMC, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90025, USA., Urushidani T; Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395, Japan., Kaunitz JD; Greater Los Angeles Veterans Affairs Healthcare System, B114, R217, West LA VAMC, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90025, USA.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2024 Apr; Vol. 69 (4), pp. 1156-1168. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1007/s10620-024-08352-6
Abstrakt: 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-HT 3 receptor agonist), apomorphine, lorglumide (CCK 1 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-CCK 1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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