Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes

• DOI: 10.1016/j.jhep.2014.05.018
• Publication Date: 2014-05-15T16:15:17Z
• Authors: Alexander König; Barbara Döring; Christina Mohr; Andreas Geipel; Joachim Geyer; Dieter Glebe
• Keywords: Ursodeoxycholic acid

The human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has recently been identified as liver-specific receptor for infection of hepatitis B virus (HBV), which attaches via the myristoylated preS1 (myr-preS1) peptide domain its large surface protein to NTCP. Since binding myr-preS1 NTCP is an initiating step HBV infection, we investigated if this process interferes with physiological transport function NTCP.HBV binding, and assays were performed primary Tupaia belangeri (PTH) (PHH) hepatocytes well NTCP-transfected hepatoma HepG2 cells allowing regulated expression, in presence various acids, ezetimibe, peptides.The inhibited PTH PHH NTCP-expressing HEK293 cells. Inversely, PTH, PHH, was a concentration-dependent manner by taurine glycine conjugates cholic ursodeoxycholic ezetimibe. In NTCP-HepG2 function, followed comparable kinetics.Myr-preS1 NTCP, necessary productive Therefore, may be lockable substrates NTCP-inhibiting drugs. This opens completely new way efficient management use NTCP-directed