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Comparison of the Effects of Two Cholecystokinin-Receptor Antagonists, Loxiglumide and L-364,718, on the Pancreatic Secretory Response to Intraduodenal Tryptophan in Dogs

E Niebergall-Roth, S Teyssen, D Wetzel, M Hartel, C Beglinger, R L Riepl, M V Singer

Scand J Gastroenterol. 1996 Jul;31(7):723-32.

PMID: 8819225

Abstract:

Background:
The aim of the study was to compare the effects of the cholecystokinin (CCK)-receptor antagonists loxiglumide and L-364, 718 on the endogenously stimulated pancreatic exocrine secretion.
Methods:
In six conscious dogs with chronic gastric and pancreatic fistulas we compared the action of different doses of loxiglumide (2.5 to 10.0 mg/kg/h) and L-364, 718 (0.025 to 0.1 mg/kg/h) on the pancreatic secretory response to intraduodenal perfusion of graded loads of tryptophan (0.37-10.0 mmol/ h), given against a background of secretin (20.5 pmol/kg/h intravenously).
Results:
Both loxiglumide and L-364, 718 inhibited the secretin-stimulated pancreatic bicarbonate output by up to 47% and 48%, respectively. The pancreatic protein output during secretin was significantly inhibited by all doses of L-364,718 (by 65% to 82%) but not by loxiglumide. All doses of loxiglumide and L-364, 718 abolished the 180-min integrated bicarbonate response to tryptophan. The two higher doses of loxiglumide (5.0-10.0 mg/kg/h) and L-364,718 (0.05-0.1 mg/kg/h) significantly decreased the 180-min integrated response to tryptophan by 59% and 79% (loxiglumide) and by 72% and 97% (L-364, 718). The plasma CCK-like immunoreactivity basally and in response to tryptophan was not significantly altered by loxiglumide or L-364, 718.
Conclusions:
These findings indicate that in dogs 1) the pancreatic bicarbonate response to secretin is augmented by the hormone CCK; 2) L-364, 718 but not loxiglumide decreases pancreatic protein output during secretin; 3) endogenous released CCK is involved in the pancreatic bicarbonate response and is a major mediator of pancreatic protein response to intraduodenal tryptophan; and 4) the release of CCK by intraduodenal tryptophan is not influenced by loxiglumide and L-364, 718.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP107097803 Loxiglumide Loxiglumide 107097-80-3 Price
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