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Am J Physiol Renal Physiol (September 16, 2003). doi:10.1152/ajprenal.00075.2003
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Submitted on February 24, 2003
Accepted on September 5, 2003

Interaction of the metal chelator, DMPS, with OAT1 and OAT3 in intact isolated rabbit renal proximal tubules

A. Lungkaphin1, V. Chatsudthipong2, K. K. Evans3, C. E. Groves3, S. H. Wright3*, and W. H. Dantzler3

1 Department of Physiology, Mahidol University, Bangkok, Thailand; Department of Physiology, University of Arizona, Tucson, AZ, USA
2 Department of Physiology, Mahidol University, Bangkok, Thailand
3 Department of Physiology, University of Arizona, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: shwright{at}u.arizona.edu.

DMPS is used clinically to increase urinary excretion of heavy metals, including mercury and arsenic. We used single S2 segments and suspensions of rabbit renal proximal tubules (RPT) to test the interaction of this anionic heavy metal chelator with basolateral transporters, OAT1 and OAT3. RT-PCR revealed expression of both transporters in single S2 segments. [3H]p-Aminohippurate ([3H]PAH), and estrone sulfate ([3H]ES) were used as specific substrates for rbOAT1 and rbOAT3, respectively. PAH and ES were transported into non-perfused single RPT segments with Kts of 67 ± 20 and 3.4 ± 1.2 µM, respectively, and into tubule suspensions with Kts of 58 ± 17 and 7.7 ± 2.1 µM, respectively. Reduced DMPS (DMPSH) inhibited uptake of both substrates into single tubule segments with Kapps of 405 ± 49 µM (for [3H]PAH) and 320 ± 66 µM (for [3H]ES). Oxidized DMPS (DMPSS), the prevalent form in the blood, also inhibited uptakes of [3H]PAH (Kapp of 766 ± 190 µM) and [3H]ES (696 ± 166 µM). Inward gradients of ES, DMPSH and DMPSS trans-stimulated the 30 sec efflux of preloaded [3H]ES across the basolateral membrane of RPT. Similarly, DMPSH, and PAH itself, trans-stimulated the 15 sec efflux of [3H]PAH. In contrast, efflux of [3H]PAH was inhibited by presence of DMPSS in the bathing medium. These data suggest that, whereas both OAT1 and OAT3 probably transport DMPSH, DMPSS transport may be limited to OAT3. This is the first evidence showing that both OAT1 and OAT3 can transport DMPS across the basolateral membrane of renal proximal tubules.




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