Rapid adaptation of pancreatic exocrine function to short-term alcohol feeding in rats.
BACKGROUND
Chronic alcohol consumption increases the risk of pancreatitis in humans. Functional hyperstimulation/hypersecretion of the pancreas during chronic alcohol consumption appears to precede the onset of pancreatitis, and may contribute to the increased susceptibility to pancreatitis in alcoholics. However, the origin, nature and timing of hyperstimulation/hypersecretion are unknown.


METHODS
Male Wistar rats were pair-fed ethanol liquid diet for 15-18 days (including one 9-day dose ramp-up phase) or regular liquid diets before placement of pancreatic, biliary, duodenal and venous catheters. Basal and stimulated pancreatic secretions were measured with or without acute alcohol infusion. Pancreatic secretion was stimulated with intravenous bethanechol, 2-deoxy-D-glucose (2-DG), cholecystokinin (CCK), octapeptide (CCK-8), intraduodenal meal, or vehicle.


RESULTS
Acute alcohol potentiated 2-DG stimulated pancreatic secretion (184%, p < 0.05), whereas the response to CCK was unchanged, and the response to bethanechol was decreased (78%, p < 0.05). Short-term alcohol exposure lessened the exaggerated protein secretory response to 2-DG seen in acute alcohol exposure rats and increased the protein response to bethanechol (141%, p < 0.05), CCK (187%, p < 0.05) and meal (217%, p < 0.05).


CONCLUSIONS
The pancreas is sensitive to acute alcohol ingestion with inhibition of acinar cell function. Rapid adaptation occurs with short-term alcohol feeding, resulting in an exaggerated response to cholinergic input at the acinar cells, plus disinhibition of CCK and meal-stimulated pancreatic secretion. The central response to 2-DG and CCK are similar to area postrema lesions. Adaptation appears to be in response to alcohol-associated inhibition of the neurohormonal stimulatory pathway and compensatory upregulation at the acinar cell level.
Deng
Xiaoying
X
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Wood
Paul G
PG
Eagon
Patricia K
PK
Whitcomb
David C
DC
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000428:Alcohol Drinking / Q000503:physiopathology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D004386:Duodenum; D004435:Eating; D000431:Ethanol / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D018721:Muscarinic Agonists / Q000494:pharmacology; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000502:physiology
D000963:Antimetabolites; D002492:Central Nervous System Depressants; D018721:Muscarinic Agonists; D018723:Bethanechol; D000431:Ethanol; D003847:Deoxyglucose