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Influence of gastric acid on gastric emptying and gastric distension-induced pain response in rats – effects of famotidine and mosapride

Authors


Address for Correspondence
Dr. Yoshihiro Keto, Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Tel: +81 29 863 6658; fax: +81 29 852 2955;
e-mail: yoshihiro.keto@jp.astellas.com

Abstract

Background  Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD.

Methods  In the present study, we determined the influence of pentagastrin-stimulated endogenous gastric acid on gastric emptying and GD-induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD-induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD-induced increase in mean blood pressure occurred.

Key Results  Pentagastrin (2 mg kg−1, s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline-injected groups. Oral famotidine (0.1–3 mg kg−1) and mosapride (0.3–3 mg kg−1) administration in a dose-dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3–3 mg kg−1) significantly alleviated the aggravation of the GD-induced pain response, but mosapride (10 mg kg−1) did not.

Conclusions & Inferences  We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD-induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying.

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