Identification of phalloidin uptake systems of rat and human liver |
| |
Authors: | Meier-Abt Fabienne Faulstich Heinz Hagenbuch Bruno |
| |
Institution: | Department of Medicine, Division of Clinical Pharmacology and Toxicology, University Hospital, Ramistr. 100, CH-8091, Zurich, Switzerland. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|