A CHOLECYSTOKININ-RELEASING FACTOR MEDIATES ETHANOL-INDUCED STIMULATION OF RAT PANCREATIC-SECRETION

The mechanisms by which short-term ethanol administration alters pancr eatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. I n our studies, anesthetized as well as conscious rats were given ethan ol at a rate sufficient to cause the blood ethanol concentration to re ach levels associated with clinical intoxication. Ethanol was administ ered over a 2-h period during which blood ethanol levels remained stab ly elevated. We report that intravenous administration of ethanol resu lts in a transient increase in pancreatic amylase output and plasma ch olecystokinin (CCK) levels. The ethanol-induced increase in amylase ou tput can be completely inhibited by the CCK-A receptor antagonist L-36 4,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completel y 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 et hanol causes rat pancreatic exocrine secretion to increase. This pheno menon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to spec ulate that repeated CCK-mediated ethanol-induced stimulation of pancre atic digestive enzyme secretion may play a role in the events which li nk ethanol abuse to the development of pancreatic injury.