title: Mouse organic anion transporter 2 and 3 (mOAT2/3[Slc22a7/8]) mediates the renal transport of bumetanide.
abstract: Multispecific organic anion transporters play an important role in the excretion and the elimination of a wide variety of endogenous and exogenous substrates. To date, five murine OAT homologs such as mouse organic anion transporters 1-3, 5, and 6 (mOAT1-3, 5 and 6) have been isolated and well characterized. With the exception of mOAT6, other mOAT isoforms are predominantly expressed in the kidney. The aim of this study was to examine whether mOAT2/3, as well as hOAT2/3, transports the diuretic bumetanide using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, mOAT2/3 mediated the high affinity transport of bumetanide. The apparent K(m) values for the uptake of bumetanide via mOAT2 and mOAT3 were 9.12 +/- 2.42 microM and 1.01 +/- 0.27 microM, respectively. Immunohistochemical analysis revealed that mOAT2 is expressed on the luminal membrane site of the proximal tubule. Our results indicate that mOAT2 and 3, as well as human homologs, are molecules for the transport of bumetanide on the luminal membranes of kidney proximal tubules.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohbayashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Kohyama
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001692:Biological Transport; D002034:Bumetanide / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D014316:Tritium; D014982:Xenopus laevis
chemical_list: D029362:Organic Anion Transporters, Sodium-Independent; C490281:Slc22a7 protein, mouse; C114338:organic anion transport protein 3; D002034:Bumetanide; D014316:Tritium