Proteases and protease inhibitors in cerulein-induced acute pancreatitis in rats.
BACKGROUND
Proteases and protease inhibitors are important in acute pancreatitis (AP), although little is known about the time course in cerulein-induced AP in the rat.


METHODS
AP was induced by supramaximal stimulation of cerulein, 10 microgram/kg/h, and during 72 h we measured lipase, amylase, albumin, prekallikrein, factor X, alpha(1)-protease inhibitor, alpha(1)-macroglobulin, alpha(2)-antiplasmin, antithrombin III (all in plasma) and macroscopic and histologic variables.


RESULTS
Within 12 h an edematous pancreatitis was evident with peak values of peritoneal exudate, pancreatic wet weight ratio, and plasma amylase and lipase activities. Histologically, edema and vacuolization were prominent already after 3 and 6 h, respectively, while inflammation, necrosis, and total histological score gradually increase to reach peak levels at 48 h. Proenzymes and most plasma protease inhibitors decreased to low levels after 6-12 h followed by a gradual increase. The sequential changes over time indicate that kallikrein - kinin activation, and plasminogen activation are probably early events in cerulein-induced AP in rats. alpha(1)-Macroglobulin and alpha(1)-protease inhibitor gradually decreased during the whole study period, probably being "second line" defense inhibitors. Levels above normal were seen for alpha(2)-antiplasmin and factor X at 48 h, normalizing at 72 h.


CONCLUSIONS
These results suggest that protease activation and protease inhibitor consumption occur in cerulein-induced AP in the rat.
Kruse
P
P
Department of Pharmacology, Copenhagen University Hospital, Glostrup, Denmark. peterkruse@dadlnet.dk
Lasson
A
A
Hage
E
E
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D002108:Ceruletide; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000097:blood*; D005170:Factor X / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008049:Lipase / Q000097:blood; D008297:Male; D010195:Pancreatitis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D011288:Prekallikrein / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D000979:alpha-2-Antiplasmin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D003174:Complement C1 Inactivator Proteins; D011480:Protease Inhibitors; D012709:Serum Albumin; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; D002108:Ceruletide; D000990:Antithrombin III; D005170:Factor X; D011288:Prekallikrein; D008049:Lipase; D000681:Amylases; D010450:Endopeptidases