Activation of trypsinogen in experimental models of acute pancreatitis in rats.
Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.
Nakae
Y
Y
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Naruse
S
S
Kitagawa
M
M
Hirao
S
S
Yamamoto
R
R
Hayakawa
T
T
D000208:Acute Disease; D000818:Animals; D001550:Benzamidines; D002108:Ceruletide; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013656:Taurocholic Acid; D014357:Trypsin / Q000097:blood / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism
D001550:Benzamidines; D006146:Guanidines; D009842:Oligopeptides; D011480:Protease Inhibitors; D011949:Receptors, Cholecystokinin; C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; C080396:trypsinogen activation peptide; D013656:Taurocholic Acid; C053737:loxiglumide; D002108:Ceruletide; D014362:Trypsinogen; D014357:Trypsin; D011377:Proglumide; C032855:nafamostat