title: Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate.
abstract: The liver plays an important role in the elimination of endogenous and exogenous lipophilic organic compounds from the body, which is mediated by various carrier proteins that differ in substrate specificity and kinetic properties. Here, we have characterized a novel member of the organic anion transporter family (SLC22) isolated from human liver. The transporter named organic anion transporter 7 (OAT7/ SLC22A9) showed 35% to 46% identities to those of other organic anion transporters of SLC22 family. When expressed in Xenopus oocytes, OAT7 mediated Na(+)-independent, high-affinity transport of sulfate-conjugated steroids, estrone sulfate (ES; K(m) = 8.7 microM), and dehydroepiandrosterone sulfate (K(m) = 2.2 microM). In addition, OAT7 interacted with negatively charged sulfobromophthalein, indocyanine green, and several sulfate-conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on OAT7-mediated [(3)H]ES transport. OAT7-mediated [(3)H]ES transport was trans-stimulated by three-carbon to five-carbon (C3 to C5) short-chain fatty acids. The efflux of [(14)C]butyrate (C4) via OAT7 was significantly trans-stimulated by extracellular ES. Furthermore, OAT7 mediated [(14)C]butyrate uptake and [(3)H]ES efflux in exchange for extracellular butyrate both in Xenopus oocytes and OAT7-stably expressing cells. OAT7 protein was localized in the sinusoidal membrane of hepatocytes by immunohistochemical analysis.
  
  
  CONCLUSIONS
  OAT7 is the first liver-specific transporter among members of the organic anion transporters of SLC22 family. Our findings suggest a new class of substrates for organic anion transporters and provide evidence for the transport of anionic substances such as sulfate-conjugates in exchange for butyrate in hepatocytes.
authors: Department of Pharmacology and Toxicology, Kyorin University, School of Medicine, Tokyo, Japan.
authors: Ho Jung
authors: HJ
authors: Shin
authors: Naohiko
authors: N
authors: Anzai
authors: Atsushi
authors: A
authors: Enomoto
authors: Xin
authors: X
authors: He
authors: Do Kyung
authors: DK
authors: Kim
authors: Hitoshi
authors: H
authors: Endou
authors: Yoshikatsu
authors: Y
authors: Kanai
mesh_terms: D000838:Anions / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D000838:Anions; D002087:Butyrates; D005232:Fatty Acids, Volatile; D029362:Organic Anion Transporters, Sodium-Independent; C427207:SLC22A11 protein, human; D013256:Steroids; D013431:Sulfates; D015262:Xenobiotics; D004970:Estrone; C017296:estrone sulfate