Do sensory neurons mediate adaptive cytoprotection of gastric mucosa against bile acid injury?
Pretreatment with the mild irritant 1 mmol acidified taurocholate protects the gastric mucosa from the injury induced by the subsequent application of 5 mmol acidified taurocholate, a phenomenon referred to as "adaptive cytoprotection." How this occurs remains an enigma. The purpose of this study was to investigate the role of sensory neurons and mucus secretion in this phenomenon. Prior to injury with 5 mmol acidified taurocholate (pH 1.2), the stomachs of six groups of rats were subjected to the following protocol. Two groups were topically pretreated with either saline or the mild irritant 1 mmol acidified taurocholate. Two other groups received the topical anesthetic 1% lidocaine prior to pretreatment with either saline or 1 mmol acidified taurocholate. The last two groups got the mucolytic agent 10% N-acetylcysteine (NAC) after pretreatment with either saline or 1 mmol acidified taurocholate. Injury was assessed by measuring net transmucosal ion fluxes, luminal appearance of deoxyribonucleic acid (DNA), and gross and histologic injury. Pretreatment with the mild irritant 1 mmol acidified taurocholate significantly decreased bile acid-induced luminal ion fluxes and DNA accumulation, suggesting mucosal protection (corroborated by gross and histologic injury analysis). This effect was negated by lidocaine but not by NAC. Thus, it appears that sensory neurons, and not increased mucus secretion, play a critical role in adaptive cytoprotection.
Mercer
D W
DW
Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Ritchie
W P
WP
Dempsey
D T
DT
D000111:Acetylcysteine / Q000494:pharmacology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001647:Bile Acids and Salts / Q000009:adverse effects*; D004247:DNA / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000009:adverse effects
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D004247:DNA; D008012:Lidocaine; D000111:Acetylcysteine