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

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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 oeso‐phagitis. 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 m M), substance P, [β‐Ala8]‐neurokinin A 4‐10, [Sar9, Met (O2)11]‐substance P (all 10−10to 10−6 M) and capsaicin (10−8to 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 ± 0.12acid/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.