title: Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron.
abstract: The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na(+)-K(+)-ATPase (EC 3.6.3.9), secondary active Na(+)-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs. Na(+)-K(+)-ATPase was immunolocalized to the BLM along the entire human nephron. NaDC3-related immunostaining was detected in the BLM of proximal tubules and in the BLM and/or luminal membrane of principal cells in connecting segments and collecting ducts. The thin and thick ascending limbs, macula densa, and distal tubules exhibited no reactivity with the anti-NaDC3 antibody. OAT1-OAT3-related immunostaining in human kidneys was detected only in the BLM of cortical proximal tubules; all three OATs were stained more intensely in S1/S2 segments compared with S3 segment in medullary rays, whereas the S3 segment in the outer stripe remained unstained. Expression of NaDC3, OAT1, OAT2, and OAT3 proteins exhibited considerable interindividual variability in both male and female kidneys, and sex differences in their expression could not be detected. Our experiments provide a side-by-side comparison of basolateral transporters cooperating in renal OA secretion in the human kidney.
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Davorka
authors.initials: D
authors.lastname: Breljak
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Marija
authors.initials: M
authors.lastname: Ljubojević
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Systemic Physiology and Pathophysiology, University of Göttingen, Göttingen, Germany;
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Hagos
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Vedran
authors.initials: V
authors.lastname: Micek
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Daniela
authors.initials: D
authors.lastname: Balen Eror
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Ivana
authors.initials: I
authors.lastname: Vrhovac Madunić
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Brzica
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia;
authors.forename: Dean
authors.initials: D
authors.lastname: Karaica
authors.affiliation: Department of Urology, Clinical Hospital Dubrava, Zagreb, Croatia;
authors.forename: Nikola
authors.initials: N
authors.lastname: Radović
authors.affiliation: University Hospital Sisters of Mercy, Zagreb, Croatia;
authors.forename: Ognjen
authors.initials: O
authors.lastname: Kraus
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan; and.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.affiliation: Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute and Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Systemic Physiology and Pathophysiology, University of Göttingen, Göttingen, Germany;
authors.forename: Gerhard
authors.initials: G
authors.lastname: Burckhardt
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Systemic Physiology and Pathophysiology, University of Göttingen, Göttingen, Germany;
authors.forename: Birgitta C
authors.initials: BC
authors.lastname: Burckhardt
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia; sabolic@imi.hr.
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabolić
mesh_terms: D000328:Adult; D029382:Dicarboxylic Acid Transporters / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007679:Kidney Medulla / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D009399:Nephrons / Q000378:metabolism*; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D012727:Sex Characteristics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*
chemical_list: D029382:Dicarboxylic Acid Transporters; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; D029362:Organic Anion Transporters, Sodium-Independent; C092524:SLC13A2 protein, human; C490280:SLC22A7 protein, human; D027981:Symporters; C114338:organic anion transport protein 3; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Na+-K+-ATPase; Na+-dicarboxylate cotransporter 3; Western blotting; human kidney; immunocytochemistry; organic anion transporter 1; organic anion transporter 2; organic anion transporter 3; sex differences; species differences