初代培養ラット肝細胞系における肝性リパーゼ放出機構の解析に関する研究

概要

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Heparin is known to stimulate the release of hepatic hpase (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 content in the hepatocytes. In addition, the stimulatory release of HTGL activity by heparin was suppressed by cytosolic PLA_2, and 5-lipoxygenase, 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 LTB_4 production with associated of TK activity.
福山大学の論文