Phospholipase A2 stimulated release of prostanoids from the isolated, perfused rabbit liver: implications in regional cellular injury.

Abstract

We have previously demonstrated a direct relationship between the activity of the arachidonic acid cascade in vivo and the extent of cellular damage following several types of experimental injury. Since phospholipase activity has been shown to regulate arachidonic acid availability, we tested the ability of circulating phospholipase A2 (PLA2) of pancreatic origin to stimulate prostanoid production or induce cellular injury in the isolated, perfused rabbit liver. Experimental conditions were similar to those present during pancreatitis or early splanchnic artery occlusion shock. The administration of PLA2 at a rate of 100 U/min for 10 min resulted in enhanced rates of thromboxane B2 and 6-ketoprostaglandin F1 alpha release between 1 and 5 min into the infusion period. No changes in hepatic perfusion pressure, vascular resistance, wet tissue weight, or release of lactic dehydrogenase or acid phosphatase into the effluent were observed in either vehicle or PLA2-treated livers. This indicates that cellular injury was not a factor in the prostanoid release. These data suggest that circulating PLA2 can directly stimulate de novo prostanoid synthesis in noninjured tissues. Thus, enhanced plasma prostanoid concentrations in intact animals during periods or regional cellular injury may be due in part to circulating PLA2 released from damaged tissues.