Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter

S. D. Smid, A. J. Page, T. O'Donnell, J. Langman, R. Rowland, L. A. Blackshaw

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Abstract

Prolonged oesophageal acidification may impair lower oesophageal sphincter (LOS) function in reflux disease. The aim of this study was to investigate aspects of altered LOS innervation in a model of oesophagitis. Oesophagitis was induced by acid (HCl, 0.15 M) and pepsin (0.1% w/v) infusions in anaesthetized ferrets. LOS muscle strip responses to the following stimuli were measured in vitro from control and acid/pepsin-treated ferrets: electrical field stimulation (EFS; 1-50 Hz), potassium chloride KCl; 20 mM), substance P, [β-Ala8]-neurokinin A 4-10, [Sar9, Met (O2)11]-substance P (all 10-10 to 10-6 M) and capsaicin (10-8 to 10-6 M). LOS relaxation occurred in response to all stimuli except [β-Ala8]-neurokinin A 4-10, which evoked contraction. In muscle strips from acid/pepsin-treated animals there were no differences in amplitude or sensitivity of relaxation following EFS, KCl or substance P vs controls. However, the inhibitory response to capsaicin was increased four-fold (10-8 M; P < 0.05) and an increased sensitivity of the inhibitory response to [Sar9, Met (O2)11]-substance P occurred (pD2 = 8.64 ± 0.12 acid/pepsin-treated vs 7.94 ± 0.24 control, P < 0.05). We conclude that in acute oesophagitis, increased sensitivity of capsaicin-activated inhibitory pathways occurs in which activation of NK-1 receptors plays an integral role in the ferret LOS.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalNeurogastroenterology and Motility
Volume10
Issue number5
DOIs
Publication statusPublished - 1998

Keywords

  • Capsaicin-sensitive sensory neurones
  • Lower oesophageal sphincter
  • NK-1 receptor
  • Oesophagitis
  • Tachykinins

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

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