Effect of L-364,718 on GRP-stimulated pancreatic and gastric secretions and GI peptides in conscious dogs.
The effect of L-364,718, a cholecystokinin (CCK) receptor antagonist, on exocrine pancreatic secretion, gastric secretion, and plasma levels of gastrointestinal (GI) peptides stimulated by gastrin-releasing peptide (GRP) was examined in five conscious dogs. Intravenous infusion of graded doses of synthetic porcine GRP (18, 36, and 178 pmol/kg/h) caused significant and dose-dependent increases in pancreatic and gastric juice secretion and in plasma levels of pancreatic polypeptide (PP), CCK, and gastrin. Intravenous injection of L-364,718 (20 nmol/kg) significantly inhibited GRP-stimulated pancreatic outputs of juice volume, protein, and amylase and plasma PP release. L-364,718, however, did not affect gastric juice volume and plasma levels of CCK and gastrin. The results suggest that endogenously released CCK is, at least in part, responsible for GRP-stimulated pancreatic protein and enzyme secretions and PP release in dogs. The results further suggest that GRP-stimulated pancreatic secretion might be, in part, a direct response of GRP to exocrine pancreas.
Hosotani
R
R
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205.
Chowdhury
P
P
Huang
Y S
YS
McKay
D
D
Yajima
H
H
Rayford
P L
PL
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000097:blood; D020109:Devazepide; D004285:Dogs; D005750:Gastric Juice / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000097:blood*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000097:blood; D010455:Peptides / Q000494:pharmacology*
D001570:Benzodiazepinones; D005755:Gastrins; D010455:Peptides; D010191:Pancreatic Polypeptide; D019886:Gastrin-Releasing Peptide; D002766:Cholecystokinin; D020109:Devazepide