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Heparin has various actions in animal tissues, but the action mechanisms have not been fully elucidated. Here, we have investigated the stimulatory increase in the leukotriene (LT) B4 content of rat hepatocytes induced by heparin. Heparin increased the LTB4 content of the hepatocytes in a time-dependent manner up to 5 min; its maximal effect was three-fold higher than the basal level of LTB4. When tyrosine kinase (TK) activity in the membrane-containing preparation of the hepatocytes was suppressed, the stimulatory increase in LTB4 by heparin was markedly reduced. It was also observed that the heparin-stimulated increase in LTB4 was reduced by various cytosolic phospholipase A2 (PLA2) inhibitors. These findings suggest that heparin stimulates a rapid increase in LTB4 in rat hepatocytes, and that this increase is partly due to an action involving the membrane TK- and the cytosolic PLA2-sensitive pathways.

Rapid Increase in the Leukotriene B4 Concentration of Cultured Rat Hepatocytes by Heparin