PHYSIOLOGICAL CONTROL OF CHOLECYSTOKININ RELEASE AND PANCREATIC-ENZYME SECRETION BY INTRADUODENAL BILE-ACIDS

Background-The physiological relevance of duodenal bile acids in contr ol of cholecystokinin release and pancreatic enzyme secretion is still unknown. Aim-To-provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid compo sition of the person under investigation. For maximal reduction of end ogenous bile output the CCK-A receptor antagonist loxiglumide was infu sed intravenously. Subjects and Methods-Seven healthy volunteers were studied on four different days by a duodenal marker perfusion techniqu e. The individual bile acid composition in duodenal juice and test mea l stimulated bile acid output was assessed on day 1. Bile acids were p erfused at an amount of 30 or 100% as determined on day 1 in combinati on with the test meal in the presence or absence of loxiglumide. Pancr eatic enzymes, bilirubin, and bile acid output were determined in duod enal juice. Plasma cholecystokinin (CCK) and plasma pancreatic polypep tide (PP) were measured radioimmunologically. Results-Bile acid perfus ion did not significantly alter stimulated pancreatic enzyme, bilirubi n or bile acid output or plasma CCK. Loxiglumide did not alter basal C CK release but increased test meal stimulated CCK output fourfold (p<0 . 05). The addition of bile acids to the test meal at a dose resembli ng 30% of bile acid output as determined on day 1 prevented this incre ase. Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion. Conclusion-The CCK p roducing cell is under constant suppression by intraduodenal bile acid s which cannot be further enhanced by a physiological bile acid mixtur e. However, removal of duodenal bile acids by inhibition of gall bladd er contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels. As little as one third of postprandially releas ed bile acids completely reverse this effect. Bile acids are the most important luminal regulator of CCK release in humans.