Platelet-activating factor mediates pancreatic function derangement in caerulein-induced pancreatitis in rats.
1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 micrograms/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis. 2. We have also observed the effect of the platelet-activating factor antagonist, BN-52021, on the hyperamylasaemia and exocrine pancreatic secretion impairment associated with pancreatitis. 3. In rats with pancreatitis the basal pancreatic flow rate was increased (1.63 +/- 0.41 versus 0.25 +/- 0.03 microliters/min). Total protein output was similar in both untreated (5.98 +/- 1.93 micrograms/min) and caerulein-injected (6.5 +/- 2.0 micrograms/min) animals. Amylase output was lower in rats with pancreatitis (19.6 +/- 4.8 mu-units/min) than in controls (39.4 +/- 16.6 mu-units/min). 4. Caerulein-treated animals had significantly higher serum amylase levels than untreated animals. BN-52021 significantly reduced the caerulein-induced hyperamylasaemia. 5. Portal blood platelet-activating factor levels increased in rats with pancreatitis and in rats infused with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood levels of platelet-activating factor that were lower than those with pancreatitis. 6. Morphological derangements associated with pancreatitis (inflammatory infiltration and cell vacuolization) were also markedly reduced in BN-52021-treated animals. 7. The results of this study suggest that platelet-activating factor is involved in the development of caerulein-induced acute pancreatitis in rats.
Alonso
R
R
Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Spain.
Montero
A
A
Arévalo
M
M
García
L J
LJ
Sánchez-Vicente
C
C
Rodríguez-Nodal
F
F
López-Novoa
J M
JM
Calvo
J J
JJ
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D002108:Ceruletide; D002766:Cholecystokinin / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000503:physiopathology*; D010195:Pancreatitis / Q000097:blood / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D002108:Ceruletide; D002766:Cholecystokinin; C045856:ginkgolide B; D000681:Amylases