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Previous experiments in Oat1 knockout (\u2212\/\u2212) mice revealed an almost complete loss of renal secretion of the prototypic organic anion p-aminohippurate (PAH) and a role of OAT1 in tubular secretion of furosemide (Eraly SA, Vallon V, Vaughn D, Gangoiti JA, Richter K, Nagle M, Monte JC, Rieg T, Truong DM, Long JM, Barshop BA, Kaler G, Nigam SK. J Biol Chem 281: 5072\u20135083, 2006). In this study we found that both furosemide and bendroflumethiazide inhibited mOat1- and mOat3-mediated uptake of a labeled tracer in Xenopus oocytes injected with cRNA, consistent with their being substrates for mouse OAT1 and OAT3. Experiments in Oat3<jats:sup>\u2212\/\u2212<\/jats:sup>mice revealed intact renal secretion of PAH, but the dose-natriuresis curves for furosemide and bendroflumethiazide were shifted to the right and urinary furosemide excretion was impaired similar to the defect in Oat1<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Thus, whereas OAT1 (in contrast to OAT3) is the classic basolateral PAH transporter of the proximal tubule, both OAT1 and OAT3 contribute similarly to normal renal secretion of furosemide and bendroflumethiazide, and a lack of either one is not fully compensated by the other. Although microarray expression analysis in the kidneys of Oat1<jats:sup>\u2212\/\u2212<\/jats:sup>and Oat3<jats:sup>\u2212\/\u2212<\/jats:sup>mice revealed somewhat altered expression of a small number of transport-related genes, none were common to both knockout models. When searching for polymorphisms involved in human diuretic responsiveness, it may be necessary to consider both OAT1 and OAT3, among other genes.<\/jats:p>","DOI":"10.1152\/ajprenal.00528.2007","type":"journal-article","created":{"date-parts":[[2008,1,24]],"date-time":"2008-01-24T01:35:53Z","timestamp":1201138553000},"page":"F867-F873","source":"Crossref","is-referenced-by-count":123,"title":["Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics"],"prefix":"10.1152","volume":"294","author":[{"given":"Volker","family":"Vallon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Rieg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish A.","family":"Eraly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Nigam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00619.2004"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1159\/000074539"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0398-1"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5722"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.6.620"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1007\/s10254-002-0003-8"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Burckhardt G, Bahn A, Wolff NA.Molecular physiology of renalp-aminohippurate secretion.News Physiol Sci16: 114\u2013118, 2001.","DOI":"10.1152\/physiologyonline.2001.16.3.114"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.5.1277"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200309000-00011"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.3.479"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508050200"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(02)00633-8"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Hasannejad H, Takeda M, Taki K, Shin HJ, Babu E, Jutabha P, Khamdang S, Aleboyeh M, Onozato ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H.Interactions of human organic anion transporters with diuretics.J Pharmacol Exp Ther308: 1021\u20131029, 2004.","DOI":"10.1124\/jpet.103.059139"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005090966"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.3.746"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.1.F122"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000120368.59693.A8"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.136"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1089-9"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Kojima R, Sekine T, Kawachi M, Cha SH, Suzuki Y, Endou H.Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney.J Am Soc Nephrol13: 848\u2013857, 2002.","DOI":"10.1681\/ASN.V134848"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.19.13675"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.3.1519"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00029.2004"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.10.6471"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01325-2"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui K.Gene expression levels and immunolocalization of organic ion transporters in the human kidney.J Am Soc Nephrol13: 866\u2013874, 2002.","DOI":"10.1681\/ASN.V134866"},{"key":"R27","doi-asserted-by":"crossref","unstructured":"Nigam SK, Bush KT, Bhatnagar V.Drug and toxicant handling by the OAT organic anion transporters in the kidney and other tissues.Nat Clin Pract Nephrol3: 443\u2013448, 2007.","DOI":"10.1038\/ncpneph0558"},{"key":"R28","unstructured":"Richterich R.Clinical Chemistry, edited by Raymond S and Wikinson JH. 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