The effects of sustained, high blood alcohol levels (216 ± 120 mg/100 ml, S.D.) for 30 days on cholecystokinin (CCK)-mediated pancreatic exocrine function were studied in a rat model that achieves both maximally controlled, optimal nutrition and high alcohol intake (∼40.5% of total calories). In alcohol-fed rats, basal plasma levels of immunoreactive cationic trypsinogen (ICT) were reduced by 50% (P < 0.05), but intravenous doses (0-30 IDU/kg/hr; 1 IDU = ∼62.5 ng CCK-8) of cholecystokinin octapeptide (CCK-8) resulted in a 3-fold greater maximal concentration of ICT and an 80% steeper slope of the dose-response curve compared to those of pair-fed control animals. Basal plasma levels of amylase were not different in the two groups at basal conditions and did not change significantly following CCK-8 administration. In vitro studies with isolated pancreatic acini have shown that basal secretion of ICT into the media was similar in the two groups. However, ICT secretion in response to CCK-8 (30-3000 pM) was 2-fold greater in alcohol-fed rats than in pair-fed controls, resulting in a CCK-8ec50 which was about half that of controls. On the contrary, the basal and maximal amylase secretion from acini isolated from alcohol-fed rats was reduced by 67 and 43%, respectively, causing a reduction in the magnitude of the response curve with almost identical ec50 and slopes. Despite the marked alterations in CCK-stimulated enzyme secretion, radioiodinated CCK-33 binding to receptors on acini isolated from both control and alcohol-fed rats was similar. Cellular concentrations of ICT and amylase, however, revealed similar patterns of alterations: 2 to 3-fold increase in ICT and 70% reduction in amylase in alcoholic acini compared to controls. These results indicate that the inverse changes in amylase and ICT secretions following continuous ethanol administration are probably due to differential effects on enzyme synthesis.
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