Afferent Signalling from the Acid-challenged Rat Stomach is Inhibited and Gastric Acid Elimination is Enhanced by Lafutidine

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2009 Jun 4

PMID 19490646

Citations 3

Authors

Martin E Edelsbrunner

Motoko Nakano

Peter Holzer

Affiliations

Soon will be listed here.

Abstract

Background: Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge.

Methods: Adult rats were treated with vehicle, lafutidine (10 - 30 mg/kg) or cimetidine (10 mg/kg), and 30 min later their stomachs were exposed to exogenous HCl (0.25 M). During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry.

Results: Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects.

Conclusion: These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect the gastric mucosa from acid injury independently of their ability to suppress gastric acid secretion.

Citing Articles

Neural Mechanisms That Underlie Angina-Induced Referred Pain in the Trigeminal Nerve Territory: A c-Fos Study in Rats.

Hayashi B, Maeda M, Tsuruoka M, Inoue T ISRN Pain. 2016; 2013:671503.

PMID: 27335881 PMC: 4893399. DOI: 10.1155/2013/671503.

Efficacy of Lafutidine Versus Famotidine in Patients with Reflux Esophagitis: A Multi-Center, Randomized, Double-Blind, Non-inferiority Phase III Trial.

Kim E, Lee Y, Chang Y, Park J, Chun H, Jung H Dig Dis Sci. 2014; 60(6):1724-32.

PMID: 25532503 DOI: 10.1007/s10620-014-3489-4.

Common brain activations for painful and non-painful aversive stimuli.

Hayes D, Northoff G BMC Neurosci. 2012; 13:60.

PMID: 22676259 PMC: 3464596. DOI: 10.1186/1471-2202-13-60.

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