Therapeutic and protective effect of subcutaneous injections of L-364,718 on caerulein-induced acute pancreatitis.
The prophylactic and therapeutic effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on acute pancreatitis induced by caerulein were evaluated, analyzing morphologic and functional pancreatic parameters jointly. Edematous pancreatitis was induced by four subcutaneous injections of caerulein (20 micrograms/kg) in rats at 1-h intervals. Prophylactic administration of L-364,718 (0.1 mg/kg) prevented rise in serum amylase levels, interstitial edema, vacuolization, and impairment of pancreatic enzyme secretion that accompany caerulein-induced acute pancreatitis. After 7 days, a spontaneous regression of the morphologic alterations caused by caerulein-induced acute pancreatitis occurs; however, recovery of the secretory function of the pancreas was only reached after this period of time when L-364,718 was administered therapeutically (0.1 mg/kg/day). Prophylactically or therapeutically administered, L-364,718 exerts a beneficial effect on caerulein-induced acute pancreatitis, indicating that CCK (exogenous or endogenous) plays an important role in the development of this pathology.
Garcia-Montero
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AC
Department of Physiology and Pharmacology, Faculty of Biology, University of Salamanca, Spain.
Manso
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MA
Rodriguez
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AI
De Dios
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I
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000627:therapeutic use*; D002108:Ceruletide; D020109:Devazepide; D007279:Injections, Subcutaneous; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000378:metabolism
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002108:Ceruletide; D000681:Amylases; D014357:Trypsin; D020109:Devazepide