Aspirin inhibits secretagogue-stimulated and postprandial pancreatic exocrine secretion in conscious rats.
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.
Li
P
P
Department of Medicine, School of Medicine and Dentistry, University of Rochester, New York.
Zhou
L
L
Levine
R A
RA
Chey
W Y
WY
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
D012459:Salicylates; D012633:Secretin; D002766:Cholecystokinin; D015232:Dinoprostone; D020156:Salicylic Acid; D001241:Aspirin; D007213:Indomethacin