title: Effect of the cholecystokinin-receptor antagonist lorglumide on pancreatic enzyme secretion stimulated by bombesin, food, and caerulein, giving similar plasma cholecystokinin concentrations in the dog.
abstract: This study was undertaken to determine the role of cholecystokinin in pancreatic enzyme secretion stimulated by bombesin and a meal by (a) comparing the pancreatic enzyme output during bombesin infusion and after a meal to output during caerulein infusion and (b) comparing the inhibitory effect of the cholecystokinin-receptor antagonist lorglumide (CR-1409) on enzyme output in response to bombesin and food with the response to caerulein. Bombesin (90 pmol/kg per h) and caerulein (30 pmol/kg per h) were infused into seven dogs in doses giving similar plasma cholecystokinin peak increments as a meal (mean (SEM) 6.8 (0.8), 6.3 (1.2), and 5.7 (0.8) pM, respectively), together with either saline or 2 mg/kg per h of lorglumide. A background infusion of synthetic secretin 20.5 pmol/kg per h was given in each experiment. In addition, gastric acid secretion was determined in the experiments with bombesin and caerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h) and food (1430 (220) mg/h) were similar to the responses to caerulein (1249 (201) mg/h). Lorglumide inhibited pancreatic protein output during stimulation with bombesin by 60%, after the meal by 45%, and during caerulein infusion by 68%. Pancreatic bicarbonate output by bombesin, caerulein, and food was inhibited by lorglumide by 28%, 40%, and 38%, respectively. In contrast, lorglumide significantly increased gastric acid secretion from 1.12 to 7.98 mmol/h during bombesin infusion and from 0.52 to 7.62 mmol/h during caerulein infusion. In conclusion, cholecystokinin plays an important part in the stimulation of pancreatic enzyme secretion by bombesin and a meal in conscious dogs and it is involved in the regulation of gastric acid during stimulation by infusions of caerulein and bombesin.
authors.affiliation: Department of Gastroenterology-Hepatology, University of Leiden, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: de Jong
authors.forename: M V
authors.initials: MV
authors.lastname: Singer
authors.forename: J B
authors.initials: JB
authors.lastname: Jansen
authors.forename: W
authors.initials: W
authors.lastname: Niebel
authors.forename: L C
authors.initials: LC
authors.lastname: Rovati
authors.forename: C B
authors.initials: CB
authors.lastname: Lamers
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood*; D004285:Dogs; D004435:Eating / Q000502:physiology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D011506:Proteins; D002108:Ceruletide; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D001839:Bombesin