|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1998 : ¥1,800,000 (Direct Cost : ¥1,800,000)
We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transport taurocholate (Km ; 13.6 μM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17β-glucuronide and estrone-3-sulfate), eicosanoids (prostaglandin EィイD22ィエD2, thromboxane BィイD22ィエD2, leukotriene CィイD24ィエD2, leukotriene EィイD24ィエD2), and thyroid hormones, reflecting hepatic multispecificity. LST-1 is probably the most important transporter in the human liver for clearance of bile acids and organic anions since hepatic levels of another organic anion transporter, OATP is very low. We have also isolated rat counter part, rlst-1. Rlst-1 is excusively expressed in the liver and in both the bile duct ligation model and the cecum ligation and puncture model, the mRNA expression levels of rlst-1 were down-regulate, suggesting rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.