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


METHODS
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).


RESULTS
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.
Niebergall-Roth
E
E
Department of Medicine IV (Gastroenterology), University Hospital of Heidelberg at Mannheim, Germany.
Teyssen
S
S
Hartel
M
M
Beglinger
C
C
Riepl
R L
RL
Singer
M V
MV
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002766:Cholecystokinin / Q000097:blood / Q000276:immunology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D014364:Tryptophan / Q000008:administration & dosage / Q000494:pharmacology*
D001639:Bicarbonates; D012633:Secretin; D014364:Tryptophan; D002766:Cholecystokinin