Inhibitory effect of CR-1409, a competitive inhibitor of cholecystokinin, on pancreatic exocrine secretion in the conscious rat.

The inhibitory effect of CR-1409, a new glutaramic acid derivative and a competitive inhibitor for cholecystokinin (CCK), on the basal and CCK-stimulated pancreatic secretion was examined in the conscious rat in vivo. Rats were prepared with cannulae draining pure bile and pancreatic juice separately and with a duodenal cannula and right and left jugular vein cannulae. Plasma CCK level increased to 3.65 +/- 0.79 and 19.9 +/- 4.47 pM (mean +/- S.E.) by a 2-hr infusion of 100 and 300 pmole/kg/hr of CCK-octapeptide (CCK-8), respectively. Simultaneous infusion of 170 nmole/kg/hr of CR-1409 completely abolished pancreatic responses to 100 pmole/kg/hr of CCK-8. Infusion of CR-1409 at rate of 57 nmole/kg/hr slightly but significantly inhibited CCK-8 (100 pmole/kg/hr)-stimulated secretion. Pancreatic responses to 300 pmole/kg/hr of CCK-8 were partially inhibited but not completely abolished by the 170 nmole/kg/hr of CR-1409. Neither the basal pancreatic secretion nor the bile secretion was affected by CR-1409. We conclude that CR-1409 inhibited CCK-stimulated pancreatic secretion in vivo.