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

• Published in: Gut 1991-02, Vol.32 (2), p.215-219
• Main Authors: de Jong, A J, Singer, M V, Jansen, J B, Niebel, W, Rovati, L C, Lamers, C B
• Format: Article
• Language: English
• Subjects: Animals; Bicarbonates - metabolism; Biological and medical sciences; Bombesin - pharmacology; Ceruletide - pharmacology; Cholecystokinin - antagonists & inhibitors; Cholecystokinin - blood; Dogs; Eating - physiology; Exocrine pancreas; Female; Fundamental and applied biological sciences. Psychology; Gastric Acid - metabolism; Pancreas - enzymology; Proglumide - analogs & derivatives; Proglumide - pharmacology; Proteins - metabolism; Vertebrates: digestive system
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.32.2.215

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.