title: Control of interdigestive and intraduodenal meal-stimulated pancreatic secretion in rats.
abstract: Mechanisms of neural (vagal and cholinergic) and hormonal [cholecystokinin (CCK)] control of pancreatic exocrine secretion were studied in basal interdigestive conditions and after stimulation by an intraduodenal meal in rats equipped with a semichronic pancreatic fistula. Bile was recirculated into the duodenum, and a solution of trypsin and electrolytes was continuously infused. Pancreatic secretion was compared in control experiments, after vagotomy, and after venous infusion of cholinergic and CCK antagonists. Basal pancreatic secretion was decreased by atropine, pirenzepine, and hexamethonium and to a lesser extent by vagotomy (protein output decreased more than fluid and HCO3- outputs). The CCK antagonists L364,718 and lorglumide had no effect on basal interdigestive pancreatic secretion. Small doses of atropine (8 and 25 micrograms.kg-1.h-1) did not modify the cumulated pancreatic response to the meal, whereas larger doses (75 and 225 micrograms.kg-1.h-1) increased it by 40-85%, according to the variables. Pirenzepine and hexamethonium did not modify the pancreatic response. Vagotomy had no effect on fluid and HCO3- responses and tended to increase protein response. L364,718 and lorglumide completely inhibited the protein response and decreased the fluid and HCO3- responses by 75 and 40%, respectively. L364,718 also suppressed the increased pancreatic response induced by atropine. This work confirms the prominent role of neural cholinergic mechanisms in the control of basal interdigestive pancreatic secretion in rats. In contrast, the pancreatic protein response to an intraduodenal meal depends on CCK, whereas fluid and HCO3- responses also depend on other hormonal factors. Our results suggest that a muscarinic (probably M3) mechanism can decrease the postprandial CCK release independently of the pancreatic feedback control by trypsin.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U239, Faculté Xavier Bichat, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Chariot
authors.forename: C
authors.initials: C
authors.lastname: Nagain
authors.forename: F
authors.initials: F
authors.lastname: Hugonet
authors.forename: A
authors.initials: A
authors.lastname: Tsocas
authors.forename: C
authors.initials: C
authors.lastname: Rozé
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D004063:Digestion / Q000187:drug effects; D004386:Duodenum / Q000502:physiology*; D004435:Eating; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014628:Vagotomy
chemical_list: D001570:Benzodiazepinones; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D010890:Pirenzepine; D001285:Atropine; D002766:Cholecystokinin; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide