Sphincter of Oddi function in the Australian brush-tailed possum is inhibited by intragastric ethanol.
The role of sphincter of Oddi (SO) function in alcoholic acute pancreatitis (AP) is unclear. We aimed to compare the effect of i.v. and intragastric (IG) ethanol on SO function (i.e. trans-sphincteric flow; TSF) and investigate possible neural mechanisms. The involvement of gastric mucosal damage was also investigated by pretreatment with pantoprazole. In anaesthetized Australian possums, blood pressure (BP), TSF and blood ethanol concentrations were measured after i.v. or IG ethanol. Possums were subjected to acute vagotomy, atropine, L-nitro arginine methyl ester (L-NAME) or pantoprazole pretreatment prior to IG ethanol. BP was not significantly altered by ethanol. Ethanol decreased TSF in a dose and route-dependent manner. The lowest dose of IG ethanol reduced TSF but this response was not duplicated by i.v. ethanol producing the same blood ethanol concentrations. Acute vagotomy, atropine or L-NAME pretreatment blocked the ethanol-induced decrease in TSF and simultaneously suppressed the blood ethanol concentration. Pantoprazole pretreatment reduced the TSF response and blood ethanol concentrations implicating mechanisms induced by gastric mucosal damage. We conclude that ethanol (and/or its metabolites) reduces TSF via humoral and neural mechanisms involving vagal pathways, muscarinic receptors and nitric oxide. Reduced TSF could contribute to the onset of AP.
Sonoda
Y
Y
Pancreatobiliary Research Group, Department of General and Digestive Surgery, Flinders University, Flinders Medical Centre, Bedford Park, Australia.
Kawamoto
M
M
Woods
C N
CN
Schloithe
A C
AC
Carati
C J
CJ
Toouli
J
J
Saccone
G T P
GT
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077402:Pantoprazole; D010276:Parasympatholytics / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D048330:Trichosurus; D014628:Vagotomy
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D010276:Parasympatholytics; D000431:Ethanol; D001285:Atropine; D000077402:Pantoprazole; D019001:Nitric Oxide Synthase