Effects of M1 and CCK antagonists on latency of pancreatic amylase response to intestinal stimulants

In six conscious dogs with gastric and duodenal cannulas, secretin (164 pmo l . kg(-1) . h(-1) iv) was given to provide a flow of pancreatic juice of s imilar to 1 drop/s. Amylase activity was measured in each drop before and a fter rapid intravenous injection of caerulein (7.4 pmol/kg) or intraduodena l injection of L-tryptophan (1 mmol), sodium oleate (3 mmol), and HCl (3 mm ol). All experiments were repeated in the presence of the M1 receptor antag onist telenzepine (81 nmol . kg(-1) . h(-1) iv) and the cholecystokinin (CC K) receptor antagonist L-364718 (0.1 mg/kg iv). Latency of amylase response (time between injection of stimulant and sustained increase in amylase act ivity greater than mean + 3 SD of prestimulatory activity) to tryptophan (1 7 +/- 7 s; n = 6) and oleate (16 +/- 5 s) was significantly (P < 0.05) shor ter than to caerulein (28 +/- 4 s) and HCl (120 +/- 47 s). Telenzepine sign ificantly increased the latency of amylase response to tryptophan and oleat e by >10-fold but not the latency to caerulein or HCl. L-364718 abolished t he amylase response to all stimulants. These findings indicate that the ear ly amylase response to intraduodenal tryptophan and oleate is mediated by a neural enteropancreatic reflex ending on M1 receptors rather than by hormo ne release. However, the activation of (possibly vagal) CCK receptors is es sential to run the reflex. The early amylase response to intraduodenal HCl is probably mediated by the release of CCK into the blood circulation.