Pancreatic bicarbonate response to intraduodenal tryptophan in dogs: Role of muscarinic M1-receptors and cholecystokinin

• Published in: International journal of pancreatology 1998-02, Vol.23 (1), p.31-39
• Main Authors: NIEBERGALL-ROTH, E, TEYSSEN, S, HARTEL, M, BEGLINGER, C, RIEPL, R. L, SINGER, M. V
• Format: Article
• Language: English
• Subjects: Animals; Bicarbonates - metabolism; Biological and medical sciences; Cholecystokinin - blood; Cholecystokinin - immunology; Dogs; Female; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Liver. Bile. Biliary tracts; Male; Pancreas - drug effects; Pancreas - metabolism; Secretin - pharmacology; Tryptophan - administration & dosage; Tryptophan - pharmacology; Vertebrates: digestive system
• ISSN: 0169-4197; 2363-5134
• DOI: 10.1007/BF02787501

In dogs, 1. Activation of cholecystokinin-receptors is needed for an adequate pancreatic bicarbonate response to secretin; 2. Cholinergic nerve fibers ending on M1-receptors are probably of little or no importance for the bicarbonate response to secretin in the given dose; 3. The bicarbonate response to tryptophan, given with a secretin background, is controlled by cholinergic M1-fibers and by cholecystokinin; 4. M1-fibers mainly mediate the bicarbonate response to low loads of tryptophan, whereas cholecystokinin controls the response to low and high loads of tryptophan; and 5. Both mediators interact in a synergistic manner. In six conscious dogs with chronic gastric and duodenal fistulas, we compared the action of the M1-receptor antagonist telenzepine (20.25-81.0 nmol/kg/h), the cholecystokinin-receptor antagonist L-364,718 (0.025-0.1 mg/kg/h), and combinations of both on the pancreatic bicarbonate response to graded loads of intraduodenal tryptophan (0.37-10.0 mmol/h), given against a background of secretin (20.5 pmol/kg/h). Secretin significantly (p < 0.05) stimulated the pancreatic bicarbonate output above basal levels. All doses of L-374,718, but not telenzepine, significantly decreased the bicarbonate response to secretin by up to 64%. Additional administration of telenzepine together with L-364,718 had no further inhibitory effect on the secretin-stimulated bicarbonate output as compared to L-364,718 given alone. All loads of tryptophan significantly increased the bicarbonate output over that seen with secretin alone (= incremental bicarbonate response to tryptophan). Telenzepine significantly decreased the incremental bicarbonate response to the two lower loads (0.37-1.1 mmol/h) of tryptophan (by 82-124%); L-364,718 decreased the incremental bicarbonate response to all loads of tryptophan (by 50-118%). The incremental bicarbonate output, as well as the 180-min integrated bicarbonate response to all loads of tryptophan, were abolished by all combinations of both antagonists.