![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 60, Issue 5, 1091-1099, November 2001
Departments of Environmental Medicine (J.M.P., A.G., L.L., N.B.)
and Pharmacology and Physiology (M.F.W., M.W.A.), University of
Rochester School of Medicine and Dentistry, Rochester, New York; and
Laboratory for Pharmacology and Chemistry, National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina
(D.H.S., J.B.P.)
Mercapturic acids are N-acetyl-L-cysteine
S-conjugates that are formed from a range of endogenous
and exogenous chemicals. Although the kidney is a major site for
elimination of mercapturic acids, the transport mechanisms involved
have not been identified. The present study examined whether
mercapturic acids are substrates for the renal basolateral organic
anion transporter-1 (Oat1) from rat kidney. This carrier mediates
uptake of organic anions from the bloodstream in exchange for
intracellular 
-ketoglutarate. Uptake of
[3H]p-aminohippuric acid (PAH) in
Oat1-expressing Xenopus laevis oocytes was strongly
inhibited by
S-(2,4-dinitrophenyl)-N-acetyl-L-cysteine (DNP-NAC) and by all other mercapturic acids tested, including the
endogenous mercapturic acid N-acetyl-leukotriene
E4. Inhibition by the mercapturic acids was competitive,
which is consistent with the hypothesis that these compounds are
substrates for Oat1. This conclusion was supported by the direct
demonstration of saturable [35S]DNP-NAC uptake in
Oat1-expressing oocytes. [35S]DNP-NAC uptake was
inhibited by PAH and other mercapturic acids and was stimulated in
oocytes preloaded with glutarate. The apparent Km value for DNP-NAC uptake was only 2 µM,
indicating that this mercapturic acid is a high affinity substrate for
Oat1. Together, these data indicate that clearance of endogenous
mercapturic acids is an important function of the renal organic anion transporter.
This article has been cited by other articles:
|
|
 |
|
  N. Bakhiya, M. Batke, J. Laake, B. H. Monien, H. Frank, A. Seidel, W. Engst, and H. Glatt Directing Role of Organic Anion Transporters in the Excretion of Mercapturic Acids of Alkylated Polycyclic Aromatic Hydrocarbons Drug Metab. Dispos., October 1, 2007; 35(10): 1824 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Aslamkhan, D. M. Thompson, J. L. Perry, K. Bleasby, N. A. Wolff, S. Barros, D. S. Miller, and J. B. Pritchard The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3 Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1773 - R1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Zalups and S. Ahmad Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury: Role of Basolateral Transporter Organic Anion Transporter 1 J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2023 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wright and W. H. Dantzler Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport Physiol Rev, July 1, 2004; 84(3): 987 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pushkin, G. Carpenito, N. Abuladze, D. Newman, V. Tsuprun, S. Ryazantsev, S. Motemoturu, P. Sassani, N. Solovieva, R. Dukkipati, et al. Structural characterization, tissue distribution, and functional expression of murine aminoacylase III Am J Physiol Cell Physiol, April 1, 2004; 286(4): C848 - C856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aslamkhan, Y.-H. Han, R. Walden, D. H. Sweet, and J. B. Pritchard Stoichiometry of organic anion/dicarboxylate exchange in membrane vesicles from rat renal cortex and hOAT1-expressing cells Am J Physiol Renal Physiol, October 1, 2003; 285(4): F775 - F783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Aslamkhan, Y.-H. Han, X.-P. Yang, R. K. Zalups, and J. B. Pritchard Human Renal Organic Anion Transporter 1-Dependent Uptake and Toxicity of Mercuric-Thiol Conjugates in Madin-Darby Canine Kidney Cells Mol. Pharmacol., March 1, 2003; 63(3): 590 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Groves, L. Munoz, A. Bahn, G. Burckhardt, and S. H. Wright Interaction of Cysteine Conjugates with Human and Rabbit Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 560 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bahn, M. Knabe, Y. Hagos, M. Rodiger, S. Godehardt, D. S. Graber-Neufeld, K. K. Evans, G. Burckhardt, and S. H. Wright Interaction of the Metal Chelator 2,3-Dimercapto-1-propanesulfonate with the Rabbit Multispecific Organic Anion Transporter 1 (rbOAT1) Mol. Pharmacol., November 1, 2002; 62(5): 1128 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Koh, T. A. Simmons-Willis, J. B. Pritchard, S. M. Grassl, and N. Ballatori Identification of a Mechanism by Which the Methylmercury Antidotes N-Acetylcysteine and Dimercaptopropanesulfonate Enhance Urinary Metal Excretion: Transport by the Renal Organic Anion Transporter-1 Mol. Pharmacol., October 1, 2002; 62(4): 921 - 926. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
