Pancreatic bicarbonate response to intraduodenal tryptophan in dogs
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Activation of cholecystokinin-receptors is needed for an adequate pancreatic bicarbonate response to secretin;
Cholinergic nerve fibers ending on M1-receptors are probably of little or no importance for the bicarbonate response to secretin in the given dose;
The bicarbonate response to tryptophan, given with a secretin background, is controlled by cholinergic M1-fibers and by cholecystokinin;
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
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 antagonisttelenzepine (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 secretinstimulated 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.
Key WordsCholecystokinin dog L-364,718 M1-receptor pancreatic bicarbonate secretion telenzepine
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