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  • Title: Inhibitory effects of the cholecystokinin antagonist loxiglumide on pancreatic exocrine secretion and pancreatic growth in conscious rats.
    Author: Taguchi S, Green GM, Nakano I, Hatta Y.
    Journal: Int J Pancreatol; 1992 Apr; 11(2):67-73. PubMed ID: 1607730.
    Abstract:
    The effects of cholecystokinin (CCK) receptor antagonist Loxiglumide (CR 1505) on pancreatic exocrine secretion and growth stimulated by chronic bile-pancreatic juice diversion to the ileum were studied in conscious rats. Pancreatic secretion was measured each day at 0900 h for 7 d. Pancreatic flow and protein output were significantly increased 24 h after bile-pancreatic juice diversion. Protein output increased each successive day, reaching maximal values of 3.6-fold above basal by the 6th and 7th d of chronic bile-pancreatic juice diversion. Fluid output reached maximal values of approx. 3.5-fold above basal by the 3rd d of chronic bile-pancreatic juice diversion. Plasma CCK increased threefold above basal levels after 24 h of bile-pancreatic juice diversion and remained three- to fourfold above basal. Intragastric bolus infusion of CR 1505 (50 mg/kg) on the 7th d of chronic bile-pancreatic juice diversion inhibited pancreatic protein and fluid secretion by 80 and 75%, respectively, 60 min after administration and by 52 and 71%, respectively, 5 h later. Pancreatic wet wt after 7 d of chronic bile-pancreatic juice diversion was significantly increased by 56%, and this was completely suppressed by 50 mg/kg of CR 1505 given intragastrically every 12 h. These rests indicate that the rat with chronic bile-pancreatic juice diversion is a useful model to examine both potency and duration of the action of CCK receptor antagonists and show that CR 1505 inhibits pancreatic exocrine secretion and growth induced by endogenous CCK.
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