A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion

Ashok Saluja, L. Lu, Y. Yamaguchi, B. Hofbauer, M. Rünzi, Rajinder Dawra, M. Bhatia, M. L. Steer

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.

Original languageEnglish (US)
Pages (from-to)506-512
Number of pages7
JournalJournal of Clinical Investigation
Volume99
Issue number3
DOIs
StatePublished - Feb 1 1997
Externally publishedYes

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Keywords

  • Alcohol
  • Cholecystokinin
  • Cholecystokinin-releasing factor
  • Hormones
  • Pancreatitis

ASJC Scopus subject areas

  • Medicine(all)

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