title: Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. ma.edelsbrunner@medunigraz.at
authors.forename: Martin E
authors.initials: ME
authors.lastname: Edelsbrunner
authors.forename: Motoko
authors.initials: M
authors.lastname: Nakano
authors.forename: Peter
authors.initials: P
authors.lastname: Holzer
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000009:adverse effects / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D023421:Models, Animal; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000378:metabolism; D013270:Stomach / Q000187:drug effects* / Q000294:innervation; D013997:Time Factors
chemical_list: D000081:Acetamides; D006635:Histamine H2 Antagonists; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; C076948:lafutidine; D002927:Cimetidine; D006851:Hydrochloric Acid