Effects of a new cholecystokinin antagonist, TS-941, on experimental acute pancreatitis in rats.
The effects of a new benzodiazepine-derivative, cholecystokinin receptor antagonist, TS-941, on experimental acute pancreatitis were studied in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. Edematous pancreatitis was induced by intraperitoneal injection of 40 microg/kg body weight of cerulein at 0 and 1 h after the start of the experiment. TS-941 (3 mg/kg) was injected subcutaneously immediately and 3 h after the induction of pancreatitis. In trypsin-taurocholate-induced pancreatitis, TS-941, with or without the synthetic trypsin inhibitor ONO-3403, had no beneficial effects on the survival rate, pancreatic wet weight, and serum pancreatic enzymes. In cerulein-induced pancreatitis, the treatment with TS-941 significantly reduced the increases of pancreatic wet weight and serum amylase and lipase. Plasma trypsinogen activation peptide (TAP) significantly rose 1 h after the first injection of cerulein. TS-941 inhibited the liberation of TAP in cerulein-induced pancreatitis. These results show that TS-941 is effective for prevention of cerulein-induced edematous pancreatitis. ONO-3403 has beneficial effects on trypsin-taurocholate-induced hemorrhagic pancreatitis, but the combination of TS-941 and ONO-3403 has no additive effect.
Wang
Y
Y
Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
Naruse
S
S
Kitagawa
M
M
Ishiguro
H
H
Nakae
Y
Y
Yoshikawa
T
T
Hayakawa
T
T
D000208:Acute Disease; D000501:Allylglycine / Q000031:analogs & derivatives / Q000494:pharmacology; D000681:Amylases / Q000097:blood; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D002108:Ceruletide; D004359:Drug Therapy, Combination; D008049:Lipase / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects*; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013656:Taurocholic Acid; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D001550:Benzamidines; D009842:Oligopeptides; D011949:Receptors, Cholecystokinin; C115763:TS 941; C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; C100807:ethyl N-allyl-N-(2-methyl-3-(4-(4-amidinophenoxycarbonyl)phenyl)propenoyl)aminoacetate methanesulfonate; C080396:trypsinogen activation peptide; D000501:Allylglycine; D001569:Benzodiazepines; D013656:Taurocholic Acid; D002108:Ceruletide; D008049:Lipase; D000681:Amylases; D014357:Trypsin