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

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 anaes thetized 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, [beta-Ala(8)]-neurokinin A 4-10, [Sa(r)9, Met (O-2)(11)]-substance P (a ll 10(-10) to 10(-6) M) and capsaicin (10(-8) to 10(-6) M). LOS relaxation occurred in response to all stimuli except [beta-Ala(8)]-neurokinin A 4-10, which evoked contraction. In muscle strips from acid/pepsin-treated animal s there were no differences in amplitude or sensitivity of relaxation follo wing EFS, KCI 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 con trol, P < 0.05). We conclude that in acute oesophagitis, increased sensitiv ity of capsaicin-activated inhibitory pathways occurs in which activation o f NK-1 receptors plays an integral role in the ferret LOS.