COMPARISON OF THE EFFECTS OF THE M(1)-RECEPTOR ANTAGONIST TELENZEPINEAND THE CCK-RECEPTOR ANTAGONIST LOXIGLUMIDE ON THE PANCREATIC SECRETORY RESPONSE TO INTRADUODENAL TRYPTOPHAN IN DOGS

In six conscious dogs with chronic gastric and pancreatic fistulas we compared the action of different doses (20.25 to 81.0 nmol/kg/h) of th e muscarinic M(1)-receptor antagonist telenzepine, the cholecystokinin (CCK) antagonist loxiglumide (2.5 to 10.0 mg/kg/h) and several combin ations of both drugs on the pancreatic secretory response to intraduod enal perfusion of graded loads of tryptophan (0.37-10.0 mmol/h) given against a background of secretin (20.5 pmol/kg/h i.v.). Except for 20. 25 nmol/kg/h telenzepine, all tested doses of telenzepine and/or loxig lumide decreased the 180-min integrated bicarbonate response to trypto phan by 55 to 119%. Except of 20.25 nmol/kg/h telenzepine and/or 2.5 m g/kg/h loxiglumide, all tested doses of telenzepine and/or loxiglumide inhibited the tryptophan stimulated integrated pancreatic protein res ponse by 54 to 88%. While telenzepine mainly inhibited the bicarbonate and protein response to the lower loads of tryptophan (0.37-1.1 mmol/ h), loxiglumide decreased the response to all loads of tryptophan. The inhibition evoked by the combinations of telenzepine and loxiglumide was not significantly greater than that by single infusion of either d rug, The CCK plasma levels basally and in response to tryptophan were not significantly altered by telenzepine and/or loxiglumide. These fin dings indicate that (1) both enteropancreatic cholinergic reflexes and the hormone CCK are mediators of the protein response to intraduodena l tryptophan, (2) enteropancreatic cholinergic reflexes are probably t he dominant mediators of the response to low amounts of tryptophan, wh ereas CCK is the major mediator of the response to high loads of trypt ophan, (3) the two mediators seem to act independently of each other, and (4) the release of CCK by intestinal tryptophan is not influenced by telenzepine or loxiglumide.