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

1998; Wiley; Volume: 10; Issue: 5 Linguagem: Inglês

10.1046/j.1365-2982.1998.00118.x

1365-2982

SMID, Amanda J. Page, K.P. O’Donnell, Langman, Rowland, BLACKSHAW,

Helicobacter pylori-related gastroenterology studies

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‐Ala 8 ]‐neurokinin A 4‐10, [Sar 9 , Met (O 2 ) 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‐Ala 8 ]‐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 [Sar 9 , Met (O 2 ) 11 ] ‐ substance P occurred (pD 2 = 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.