The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats.
CONCLUSIONS
Our results suggest that the cholecystokinin (CCK) receptor antagonist L-364,718 has a protective effect on taurocholate-induced pancreatitis, and thus, it is inferred that CCK may have a significant pathophysiological role in the early phase of pancreatitis.


BACKGROUND
Conflicting results have been obtained from studies designed to determine the role of CCK in the initial stages of pancreatitis.


METHODS
We evaluated the protective effect of the CCK receptor antagonist L-364,718 (devazepide) and of the trypsin inhibitor camostat, on taurocholate-induced pancreatitis in rats. L-364,718 (1 mg/kg) or camostat (200 mg/kg) was administered intragastrically 30 min before the induction of pancreatitis.


RESULTS
Infusion of sodium taurocholate (50 mg/kg) into the pancreaticobiliary duct caused severe pancreatitis with marked hyperamylasemia and reduction of tissue enzyme content at 12 h postinfusion. Pretreatment with L-364,718, but not with camostat, caused significant improvement in signs of experimental pancreatitis based on tissue enzyme content and morphology. Compared with untreated pancreatitis, there was relatively well-preserved lobular architecture, less edema, less infiltration of inflammatory cells, and more zymogen granules after L-364,718 pretreatment. Moreover, the reduction of enzyme content owing to pancreatitis was ameliorated by L-364,718 pretreatment.
Kim
K H
KH
Department of Pharmacology, Yonsei University, College of Medicine, Seoul, Korea. Hwan444@yumc.yonsei.ac.kr
Lee
M G
MG
Kim
D G
DG
D000681:Amylases / Q000097:blood; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D020109:Devazepide; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology; D006651:Histocytochemistry; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000037:antagonists & inhibitors; D013656:Taurocholic Acid; D014361:Trypsin Inhibitors / Q000494:pharmacology
D001570:Benzodiazepinones; D002756:Cholagogues and Choleretics; D004952:Esters; D006146:Guanidines; D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; D014361:Trypsin Inhibitors; C034532:camostat; D016670:Gabexate; D013656:Taurocholic Acid; D000681:Amylases; D020109:Devazepide; D012844:Sincalide