In vivo effect of pancreatic phospholipase A2 on the arachidonic acid cascade.
BACKGROUND
In acute pancreatitis, pancreatic phospholipase A2 increases in systemic circulation. Yet the pathophysiological significance is controversial, because previous in vitro studies have shown that the enzyme has little cytotoxicity or ability to activate the arachidonic acid cascade by itself in contrast to other isozymes.


OBJECTIVE
The aims of this study are to examine the effect of pancreatic phospholipase A2 on the arachidonic acid cascade in vivo; to explain the discrepancy, if present, between in vitro and in vivo findings; and to reassess the pathophysiological significance of circulating pancreatic phospholipase A2.


METHODS
Pancreatic phospholipase A2 was infused intravenously in guinea pigs, and changes in the arachidonic acid cascade, plasma lipoprotein, and cardiopulmonary function were investigated.


RESULTS
Plasma concentrations of 6-keto-prostaglandin F1alpha, prostaglandin E2, and thromboxane B2 increased after intravenous (iv) infusion of pancreatic phospholipase A2. Some of the plasma phospholipids such as phosphatidylcholine and phosphatidylethanolamine decreased, and free dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid were detected in plasma. These changes were accompanied with decreases in blood pressure, heart rate, and base excess.


CONCLUSIONS
Circulating pancreatic phospholipase A2 activates the arachidonic acid cascade, probably by supplying free eicosanoid precursors from plasma lipoprotein to eicosanoid-producing cells. It is supposed to be a cause of systemic complications in acute pancreatitis.
Motoyoshi
M
M
Department of Surgery, Faculty of Medicine, University of Tokyo, Japan. motoyosi@juno.ocn.ne.jp
Sugiyama
M
M
Atomi
Y
Y
Kimura
W
W
Nagawa
H
H
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D008074:Lipoproteins / Q000097:blood; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000097:blood / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000097:blood
D008074:Lipoproteins; D010743:Phospholipids; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2