Comparison of two dose-response techniques to study the pancreatic secretory response to intraduodenal tryptophan in the absence and presence of the M₁-receptor antagonist telenzepine

To answer the questions if the type of continuous dose-response technique influences the pancreatic secretory response to intraduodenal tryptophan and if the Mrreceptor antagonist telenzepine influences the intestinal absorption of tryptophan, we determined, in 12 conscious dogs with chronic gastric and duodenal fistulas, pancreatic bicarbonate and protein secretion and tryptophan plasma concentrations following intraduodenal tryptophan perfusion using two dose-response techniques. With an ascending continuous dose-response technique (aDRT), tryptophan was perfused in loads ranging from 0.12 to 10.0 mmol h^-1starting with the lowest load and tripling it every 45 min. With the descending continuous dose-response technique (dDRT), the order of tryptophan loads was reversed, with the highest load being given first. All studies were done on a fixed background of intravenous secretin (20.5 pmol kg-1 h^-1) and repeated in the presence of the anticholinergic M₁receptor antagonist telenzepine (243 nmol kg^-1h^-1). The bicarbonate and protein response as well as the tryptophan plasma concentrations to the same loads of tryptophan did not differ significantly between the two techniques. Using both techniques, telenzepine significantly (p < 0.05) inhibited the overall pancreatic protein response by 65% (dDRT) to 81% (aDRT). The overall bicarbonate response was only numerically, and not statistically significantly, inhibited by telenzepine. Tryptophan plasma concentrations after duodenal perfusion with tryptophan were neither influenced by the order of tryptophan loads nor altered by telenzepine. These findings indicate that in the intact animal (a) either the aDRT or the dDRT may be used to study the pancreatic secretory response to enteral infusion of amino acids, (b) at least part of the pancreatic secretory response to tryptophan is mediated through cholinergic Mj receptors, and (c) the duodenal absorption of tryptophan is not affected by telenzepine and therefore most likely not mediated by neuronal M, receptors.