The long-term goals of the proposed research plan are to gain a better understanding of the biochemical circumstances under which chronic alcohol consumption modifies the synthesis of pancreatic digestive enzymes. The rate of synthesis of individual digestive enzymes will be compared between control and ethanol-fed rats in vivo and in vitro, in isolated acinar cell preparations. The rate of synthesis of individual digestive enzymes will be determined by studying the incorporation of labelled amino acids into proteins. Separation of individual proteins will be achieved by polyacrylamide gel-electrophoresis. The effects of ethanol ingestion on the turnover of digestive enzymes in animals that are continuously exposed to ethanol and those in which ethanol is withdrawn overnight will also be investigated. The possibility that the effects of ethanol ingestion on pancreatic protein synthesis and turnover is mediated by the release of gastrointestinal hormones such as cholecystokinin and secretin will be tested. The hypothesis that during long-term ethanol intake, the effects of such secretagogues are compensated by pancreatic inhibitors such as pancreatic polypeptide and somatostatin will also be tested. Since the composition of pancreatic digestive enzymes is known to be predominantly regulated by the composition of the diet, appropriate dietary controls will be included to distinguish specific effects of alcohol administration from those of other dietary factors. It is expected that the overall outcome of the proposed studies will provide significant new information on the susceptibilities of the pancreas to the development of pancreatitis mediated by the effects of ethanol ingestion on digestive enzyme synthesis.