EFFECTS OF CHOLECYSTOKININ RECEPTOR BLOCKADE ON PANCREATIC AND BILIARY FUNCTION IN HEALTHY VOLUNTEERS

Abstract

SummaryThe role of exogenous cholecystokinin (CCK) in the regulation of pancreatic and biliary secretions was evaluated in healthy adult volunteers using loxiglumide (formerly compound CR‐1505), a specific CCK antagonist. Gastric contents were continuously removed by aspiration and the second part of the duodenum was perfused with a mixed, liquid test meal containing a non‐absorbable marker [polyethylene glycol (PEG) 3000]. Duodenal contents were then aspirated from the region of the ligament of Treitz and levels of trypsin, chymotrypsin, amylase, bilirubin, and PEG determined by standard methods. Venous blood samples were obtained at 20 min intervals for determinations of CCK (by bioassay), insulin, and C peptide (radioimmunoassay). Gallbladder volumes were determined by ultrasonography. The ability of loxiglumide to inhibit pancreatobiliary secretion stimulated by exogenous cerulein, a CCK agonist, was also determined using similar methods.At a dose that mimics postprandial plasma CCK concentrations, loxiglumide inhibited the pancreatic and gallbladder responses to the test meal. Secretion of pancreatic enzymes was decreased by up to 75% compared with controls. Gallbladder contraction and bilirubin output were abolished. Loxiglumide also inhibited the secretion of pancreatic enzyme stimulated by exogenous cerulein. In contrast, loxiglumide failed to abolish changes in the plasma concentrations of glucose, insulin, and C peptide following the test meal.