title: Aspirin inhibits secretagogue-stimulated and postprandial pancreatic exocrine secretion in conscious rats.
abstract: The effect of salicylate and nonsalicylate antiinflammatory drugs and prostaglandins (PGs) on pancreatic exocrine secretion are controversial. We studied the effect of aspirin (ASA) on secretin- and cholecystokinin (CCK)- or meal-stimulated pancreatic secretion. The interrelation between ASA, PG, and pancreatic exocrine secretion was also investigated. Conscious rats with chronic duodenal, pancreatic, and biliary cannulas received secretin (5 pmol/kg/h, i.v.) and CCK (56 pmol/kg/h) or a meal with administration of cimetidine (20 mg/kg/h, i.v.), ASA (1.2, 12, or 60 mumol/h, i.v.), Salicylic acid (SA) (1.2, 12, or 60 mumol/h, i.v.), prostaglandin E2 (PGE2) (10 micrograms/kg/h), or indomethacin (2 mg/kg) was given, respectively. Pancreatic flow volume, bicarbonate, and protein were determined every 15 min. An inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) (36 micrograms/kg/h) and an activator, phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate, TPA) (100 ng/kg/h) were used for evaluation of the role of protein kinase C on basal and secretagogue-stimulated pancreatic secretion. ASA, but not SA inhibited the secretin- and CCK-stimulated pancreatic secretion including volume, bicarbonate, and protein in a dose-dependent manner without affecting basal pancreatic secretion. ASA and indomethacin suppressed meal-stimulated pancreatic secretion up to 83.8%. PGE2 significantly inhibited the secretin- and CCK-stimulated pancreatic secretion which was further suppressed by the concomitant ASA infusion. Modulation of protein kinase C failed to affect pancreatic secretion. The data indicate that ASA inhibits both secretin- and CCK-stimulated pancreatic secretion by a mechanism independent of prostaglandin biosynthesis inhibition.
authors.affiliation: Department of Medicine, School of Medicine and Dentistry, University of Rochester, New York.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: R A
authors.initials: RA
authors.lastname: Levine
authors.forename: W Y
authors.initials: WY
authors.lastname: Chey
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D015232:Dinoprostone / Q000494:pharmacology; D005502:Food; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D012633:Secretin / Q000037:antagonists & inhibitors*; D013268:Stimulation, Chemical
chemical_list: D012459:Salicylates; D012633:Secretin; D002766:Cholecystokinin; D015232:Dinoprostone; D020156:Salicylic Acid; D001241:Aspirin; D007213:Indomethacin