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

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  • Tagashira Hisashi
    Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
  • Kerakawati Rie
    Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
  • Motoyashiki Toshio
    Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
  • Morita Tetsuo
    Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

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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) A2 activity in the hepatocytes in a time- and dose-dependent manner. The stimulatory effect of heparin on PLA2 activity was markedly decreased by incubation with protein tyrosine kinase (TK) inhibitors. It was also observed that heparin rapidly increased leukotriene (LT) B4 and LTC4/D4/E4 contents in the hepatocytes. In addition, the stimulatory release of HTGL activity by heparin was suppressed by cytosolic PLA2, 5-lipoxygenase and LTA4 hydrolase inhibitors, but not by cyclooxygenase and thromboxane (TX) synthetase inhibitors or a TXA2 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 PLA2 activity and LTs production with associated of TK activity. <br>

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