Identification of phalloidin uptake systems of rat and human liver

Biochim Biophys Acta. 2004 Jul 1;1664(1):64-9. doi: 10.1016/j.bbamem.2004.04.004.


To determine whether the liver toxin phalloidin is transported into hepatocytes by one of the known bile salt transporters, we expressed the sodium-dependent Na+/taurocholate cotransporting polypeptide (Ntcp) and several sodium-independent bile salt transporters of the organic anion transporting polypeptide (OATP/SLCO) superfamily in Xenopus laevis oocytes and measured uptake of the radiolabeled phalloidin derivative [3H]demethylphalloin. We found that rat Oatp1b2 (previously called Oatp4 (Slc21a10)) as well as human OATP1B1 (previously called OATP-C (SLC21A6)) and OATP1B3 (previously called OATP8 (SLC21A8)) mediate uptake of [3H]demethylphalloin when expressed in X. laevis oocytes. Transport of increasing [3H]demethylphalloin concentrations was saturable with apparent Km values of 5.7 microM (Oatp1b2), 17 microM (OATP1B1) and 7.5 microM (OATP1B3). All other tested Oatps/OATPs as well as the rat liver Ntcp did not transport [3H]demethylphalloin. Therefore, we conclude that rat Oatp1b2 as well as human OATP1B1 and OATP1B3 are responsible for phalloidin uptake into rat and human hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions
  • Biological Transport
  • Dose-Response Relationship, Drug
  • Female
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Liver / drug effects*
  • Liver / metabolism*
  • Oocytes / metabolism
  • Organic Anion Transporters / physiology
  • Organic Anion Transporters, Sodium-Independent / physiology
  • Peptides / chemistry
  • Phalloidine / pharmacokinetics*
  • Rats
  • Sodium / chemistry
  • Sodium / metabolism
  • Taurocholic Acid / pharmacokinetics
  • Xenopus laevis


  • Anions
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • Peptides
  • Slco1a1 protein, rat
  • Phalloidine
  • Taurocholic Acid
  • Sodium