PANCREATIC BICARBONATE RESPONSE TO INTRADUODENAL TRYPTOPHAN IN DOGS -ROLE OF MUSCARINIC M1-RECEPTORS AND CHOLECYSTOKININ

Conclusions, In dogs, 1. Activation of cholecystokinin-receptors is ne eded for an adequate pancreatic bicarbonate response to secretin; 2. C holinergic nerve fibers ending on M-1-receptors are probably of little or no importance for the bicarbonate response to secretin in the give n dose; 3. The bicarbonate response to tryptophan, given with a secret in background, is controlled by cholinergic M-1-fibers and by cholecys tokinin; 4. M-1-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 gastri c and duodenal fistulas, we compared the action of the M-1-receptor an tagonist telenzepine (20.25-81.0 nmol/kg/h), the cholecystokinin-recep tor antagonist L-364,718 (0.025-0.1 mg/kg/h), and combinations of both on the pancreatic bicarbonate response to graded loads of intraduoden al tryptophan (0.37-10.0 mmol/h), given against a background of secret in (20.5 pmol/kg/h). Results, Secretin significantly (p < 0.05) stimul ated the pancreatic bicarbonate output above basal levels. All doses o f L-374,718, but not telenzepine, significantly decreased the bicarbon ate response to secretin by up to 64%. Additional administration of te lenzepine together with L-364,718 had no further inhibitory effect on the secretin-stimulated bicarbonate output as compared to L-364,718 gi ven alone. All loads of tryptophan significantly increased the bicarbo nate output over that seen with secretin alone (= incremental bicarbon ate response to tryptophan). Telenzepine significantly decreased the i ncremental bicarbonate response to the two lower loads (0.37-1.1 mmol/ h) of tryptophan (by 82-124%); L-364,718 decreased the incremental bic arbonate response to all loads of tryptophan (by 50-118%). The increme ntal bicarbonate output, as well as the 180-min integrated bicarbonate response to ail loads of tryptophan, were abolished by all combinatio ns of both antagonists.