Involvement of Leukotriene Production in Release of Hepatic Lipase Activity Produced by Heparin from Rat Hepatocytes

Abstract

Heparin is known to stimulate the release of hepatic lipase (HTGL) activity from hepatocytes, but the action mechanisms have not been fully confirmed. Here, we investigated the involvement of the arachidonate pathway in the heparin-stimulated release of HGTL activity from rat hepatocytes. Heparin increased phospholipase (PL) A 2 activity in the hepatocytes in a time-and dose-dependent manner. The stimulatory effect of heparin on PLA 2 activity was markedly decreased by incubation with protein tyrosine kinase (TK) inhibitors. It was also observed that heparin rapidly increased leukotriene (LT) B 4 and LTC 4 /D 4 /E 4 contents in the hepatocytes. In addition, the stimulatory release of HTGL activity by heparin was suppressed by cytosolic PLA 2 , 5-lipoxygenase and LTA 4 hydrolase inhibitors, but not by cyclooxygenase and thromboxane (TX) synthetase inhibitors or a TXA 2 receptor antagonist. These findings suggest that the heparin-stimulated release of HTGL activity from hepatocytes is partly due to an action involving increases in cytosolic PLA 2 activity and LTs production with associated of TK activity.