Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man.
To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas.
Hildebrand
P
P
Division of Gastroenterology, University Hospital, Basel, Switzerland.
Drewe
J
J
Luo
H
H
Ketterer
S
S
Gyr
K
K
Beglinger
C
C
D000328:Adult; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology
D005755:Gastrins; D005768:Gastrointestinal Hormones; D010455:Peptides; C053737:loxiglumide; D019886:Gastrin-Releasing Peptide; D002766:Cholecystokinin; D011377:Proglumide