肝細胞癌におけるホスホリパーゼC活動性細胞内情報伝達に及ぼすウルソデオキシコール酸の影響-エタノール,vasopressinによる検討-

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The effects of ursodeoxycholate (UDC) and its taurine-conjugated form TUDC on phospholipase C (PLC)-mediated intracellular signal transduction by ethanol (EtOH) and vasopressin were investigated in isolated rat hepatocytes. Vasopressin-induced PLC activation was sustained, but the response to EtOH was transient and a return to the basal value was seen at a 2 min after stimulation. Pretreatment of hepatocytes with UDC or TUDC enhanced EtOH-induced Ca2+ mobilization, but did not affect InsP3 accumulation. In contrast, both Ca2+ mobilization and InsP3 accumulation induced by vasopressin were inhibited by pretreatment with these bile acids. Pretreatment with cholate and taurocholate also inhibited the response to vasopressin. EtOH inhibited the subsequent vasopressininduced Ca2+ mobilization, and combined pretreatment of the cells with a maximum concentration of EtOH (300mM) and UDC/TUDC were additive in inhibiting the response to vasopressin, suggesting that the action sites of UDC is different from those of EtOH in hepatocytes. Thus, these results demonstrated that UDC affects PLC-mediated intracellular signal transduction in hepatocytes.