title: Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter.
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, [beta-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 [beta-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.
authors.affiliation: Gastrointestinal Medicine, Royal Adelaide Hospital, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Smid
authors.forename: A J
authors.initials: AJ
authors.lastname: Page
authors.forename: T
authors.initials: T
authors.lastname: O'Donnell
authors.forename: J
authors.initials: J
authors.lastname: Langman
authors.forename: R
authors.initials: R
authors.lastname: Rowland
authors.forename: L A
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004558:Electric Stimulation; D004941:Esophagitis / Q000139:chemically induced / Q000503:physiopathology*; D004943:Esophagogastric Junction / Q000294:innervation / Q000503:physiopathology*; D005260:Female; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology / Q000502:physiology*
chemical_list: D015320:Tachykinins; D011189:Potassium Chloride; D002211:Capsaicin