POSTPRANDIAL RELEASE OF CHOLECYSTOKININ AND PANCREATIC-POLYPEPTIDE IN HEALTH AND IN GALLSTONE DISEASE - RELATIONSHIPS WITH GALLBLADDER CONTRACTION

Objectives: The present study investigated endogenous postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in relation to gallbladder dynamics in healthy subjects and patients with gallstones. Methods: Gallbladder volume (by ultrasonography) and plasma concentrations of CCK and PP (by radioimmunoassay) were evaluated in 18 patients with gallstones and 14 healthy controls before and after administration of a semi-liquid test meal (250 ml, 1450 kJ). Gallbladder contractility was previously assessed on a separate day by intravenous infusion of ceruletide (2.5 ng/kg/min). Results: Basal gallbladder volume was not different in patients (32 +/- 5.9 cm(3)) and controls (26 +/- 2.7 cm(3)). Postprandial gallbladder contractility was impaired in gallstone patients, who showed a reduced integrated response (-3718 +/- 349 vs. -5251 +/- 376 cm(3)/2 h, p < 0.01) and a delayed time to maximal gallbladder contraction (67 +/- 7.4 min vs. 37 +/- 2.4 min, p < 0.002). Maximal gallbladder contraction after ceruletide infusion was also reduced (44.1 +/- 5.0% vs. 72.5 +/- 3.2%, p < 0.001), but not delayed (15.8 +/- 2.4 vs. 15.7 +/- 1.4 min) in gallstone patients. Basal CCK and PP plasma levels were similar in both groups. Postprandial CCK release was impaired in gallstone patients, predominantly due to a decreased response over the first 30 min (3.8 +/- 1.8 vs. 20.0 +/- 4.9 pmol/L/30 min, p < 0.005). Postprandial PP release was not different between groups. A direct linear correlation between postprandial release of CCK and PP was found in healthy controls but not in patients with gallstones. Postprandial gallbladder volume at any moment was inversely correlated with CCK plasma levels in healthy subjects, but not in gallstone patients. No correlation between postprandial PP response and gallbladder dynamics was observed. Conclusions: Based on a multivariate logistic approach, a reduced and delayed postprandial gallbladder contractility and an impaired CCK release in the early postprandial phase are significantly associated with gallstone disease. Our data provide further evidence for the predominant role of endogenous postprandial CCK release in gallbladder contraction. A role for PP in modulating postprandial gallbladder dynamics is not supported.