Effect ofthecholecystokinin- receptor antagonist lorglumide onpancreatic enzyme secretion stimulated bybombesin, food, andcaerulein, giving similar plasma cholecystokinin concentrations inthe dog

Thisstudy wasundertaken todetermine the role ofcholecystokinin inpancreatic enzyme secretion stimulated bybombesin andameal by(a)comparing thepancreatic enzyme output during bombesin infusion andafter amealto outputduring caerulein infusion and(b) comparing theinhibitory effect ofthechole- cystokinin-receptor antagonist lorglumide (CR-1409) onenzymeoutput inresponse to bombesin andfoodwiththeresponse to caerulein. Bombesin (90pmollkg perh)and caerulein (30pmollkg perh)wereinfused into sevendogsindosesgiving similar plasma cholecystokinin peakincrements asameal (mean(SEM)6.8(0.8), 6-3(1.2), and5.7(0.8) pM,respectively), together witheither saline or2mg/kg perhoflorglumide. Abackground infusion ofsynthetic secretin 20.5 pmollkg per hwasgiven ineachexperiment. Inaddition, gastric acidsecretion wasdetermined inthe experiments withbombesin andcaerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h)andfood(1430 (220) mg/h) weresimilar totheresponses to caerulein (1249(201)mg/h). Lorglumide inhibited pancreatic protein output during stimulation withbombesin by60%,after the mealby45%,andduring caerulein infusion by 68%.Pancreatic bicarbonate outputby bombesin, caerulein, andfoodwasinhibited bylorglumide by28%,40%,and38%,respec- tively. Incontrast, lorglumide significantly increased gastric acidsecretion from1.12to 7-98mmol/hduring bombesin infusion and from0.52to7.62mmol/hduring caerulein infusion. Inconclusion, cholecystokinin plays animportant partinthestimulation ofpan- creatic enzymesecretion bybombesin anda mealinconscious dogsanditisinvolved inthe regulation ofgastric acid during stimulation by infusions ofcaerulein andbombesin.