Chronic alcohol-induced alterations in the pancreatic secretory control mechanisms.
Chronic alcohol ingestion appears to increase susceptibility of the pancreas to pancreatitis through multiple mechanisms. The aim of the current study was to determine the effect of chronic low- and high-dose alcohol consumption on the neurohormonal control of the exocrine pancreas in rats. Male Wistar rats were fed Lieber DeCarli liquid control-, low-, and high-dose alcohol diets for 3 months. Pancreatic exocrine secretion was measured under basal and 2-deoxy-D-glucose (2-DG)-, CCK-, bethanechol-, or meal-stimulated conditions while on chronic alcohol diets and after 2-DG or CCK stimulation during alcohol withdrawal in awake rats. Chronic alcohol ingestion was associated with a dose-related inhibition of basal pancreatic protein secretion, which was reversed upon alcohol withdrawal. Low-dose alcohol feeding had no effect on bethanechol-stimulated pancreatic secretion but altered 2-DG-stimulated pancreatic secretion. In chronic high-dose alcohol rats, meal- and bethanechol-stimulated protein secretion was significantly potentiated during early and late phases. The response to CCK appeared to be disinhibited, whereas the response to 2-DG was uniformly blunted. Upon withdrawal of low-dose alcohol, the response to 2-DG was potentiated, whereas with the withdrawal of high-dose alcohol, the response to CCK was potentiated. Adaptation to chronic alcohol consumption differs depending on the alcohol dose. The most significant effects were seen after high-dose alcohol withdrawal, with apparent loss of central inhibitory regulation combined with exaggerated response at the acinar cell level. This combination of factors could increase susceptibility to acute alcoholic pancreatitis through a hyperstimulation mechanism.
Deng
Xiaoying
X
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Wood
Paul G
PG
Eagon
Patricia K
PK
Whitcomb
David C
DC
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005502:Food; D005765:Gastrointestinal Agents / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000438:Alcohols; D005765:Gastrointestinal Agents; D018723:Bethanechol; D000431:Ethanol; D002766:Cholecystokinin; D003847:Deoxyglucose