HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/C1075    most recent 00619.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Bahn, A. Articles by Hagos, Y. Search for Related Content PubMed PubMed Citation Articles by Bahn, A. Articles by Hagos, Y.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites

Andrew Bahn,¹ Marija Ljubojevi,² Heiko Lorenz,¹ Christian Schultz,³ Estifanos Ghebremedhin,³ Bernhard Ugele,⁴ Ivan Saboli,² Gerhard Burckhardt,¹ and Yohannes Hagos¹

¹Zentrum Physiologie und Pathophysiologie, Abt. Vegetative Physiologie und Pathophysiologie, Göttingen, Germany; ²Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, Zagreb, Croatia; ³Institut für Klinische Neuroanatomie, Universitätsklinik Frankfurt, Frankfurt; and ⁴Klinikum der Universität München, I. Frauenklinik-Innenstadt, Munich, Germany

Submitted 17 December 2004 ; accepted in final form 5 June 2005

Tryptophan metabolites such as kynurenate (KYNA), xanthurenate (XA), and quinolinate are considered to have an important impact on many physiological processes, especially brain function. Many of these metabolites are secreted with the urine. Because organic anion transporters (OATs) facilitate the renal secretion of weak organic acids, we investigated whether the secretion of bioactive tryptophan metabolites is mediated by OAT1 and OAT3, two prominent members of the OAT family. Immunohistochemical analyses of the mouse kidneys revealed the expression of OAT1 to be restricted to the proximal convoluted tubule (representing S1 and S2 segments), whereas OAT3 was detected in almost all parts of the nephron, including macula densa cells. In the mouse brain, OAT1 was found to be expressed in neurons of the cortex cerebri and hippocampus as well as in the ependymal cell layer of the choroid plexus. Six tryptophan metabolites, including the bioactive substances KYNA, XA, and the serotonin metabolite 5-hydroxyindol acetate inhibited [³H]p-aminohippurate (PAH) or 6-carboxyfluorescein (6-CF) uptake by 50–85%, demonstrating that these compounds interact with OAT1 as well as with OAT3. Half-maximal inhibition of mOAT1 occurred at 34 µM KYNA and 15 µM XA, and it occurred at 8 µM KYNA and 11.5 µM XA for mOAT3. Quinolinate showed a slight but significant inhibition of [³H]PAH uptake by mOAT1 and no alteration of 6-CF uptake by mOAT3. [¹⁴C]-Glutarate (GA) uptake was examined for both transporters and demonstrated differences in the transport rate for this substrate by a factor of 4. Trans-stimulation experiments with GA revealed that KYNA and XA are substrates for mOAT1. Our results support the idea that OAT1 and OAT3 are involved in the secretion of bioactive tryptophan metabolites from the body. Consequently, they are crucial for the regulation of central nervous system tryptophan metabolite concentration.

kidneys; brain; macula densa; transforming growth factor; N-methyl-D-aspartate receptor

This article has been cited by other articles:

				V. Vallon, S. A. Eraly, W. R. Wikoff, T. Rieg, G. Kaler, D. M. Truong, S.-Y. Ahn, N. R. Mahapatra, S. K. Mahata, J. A. Gangoiti, et al. Organic Anion Transporter 3 Contributes to the Regulation of Blood Pressure J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1732 - 1740. [Abstract] [Full Text] [PDF]

				V. Vallon, T. Rieg, S. Y. Ahn, W. Wu, S. A. Eraly, and S. K. Nigam Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics Am J Physiol Renal Physiol, April 1, 2008; 294(4): F867 - F873. [Abstract] [Full Text] [PDF]