抄録
The multispecific organic anion transporters in the liver play an important role in the elimination of toxic substances and in the turnover of endogenous biomolecules. In this study, we functionally characterized a novel organic anion transporter OAT7 (SLC22A9) exclusively expressed in human liver. When expressed in Xenopus oocytes, OAT7 mediated high affinity transport of sulfate-conjugated steroid hormones, estrone sulfate (ES) (Km = 8.7 μM) and DHEA sulfate (Km = 2.2 μM), in a sodium independent manner. ES transport mediated by OAT7 was inhibited by negatively charged BSP, ICG and several sulfate-conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on the OAT7-mediated transport. Immunohistochemical analysis revealed that OAT7 protein was located in the sinusoidal membrane of hepatocytes. We further examined the trans-stimulatory effects of various endogenous organic anions to investigate the driving force for OAT7-mediated transport. Short chain fatty acids trans-stimulated the OAT7-mediated ES uptake by the injection of those cold compounds into the oocytes. Furthermore, OAT7 mediated [14C]butyrate uptake and [3H]ES efflux in exchange for extracellular butyrate both in Xenopus oocytes and OAT7-stably expressing cells. These results suggest that OAT7 is the liver-specific organic anion transporter using butyrate as a counterion for its transport of steroid sulfates. [J Physiol Sci. 2008;58 Suppl:S22]
