Publication: Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules
Issued Date
2004-11-01
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ISSN
03636127
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2-s2.0-6344289334
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Renal Physiology. Vol.287, No.5 56-5 (2004)
Suggested Citation
S. Soodvilai, V. Chatsudthipong, K. K. Evans, S. H. Wright, W. H. Dantzler Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules. American Journal of Physiology - Renal Physiology. Vol.287, No.5 56-5 (2004). doi:10.1152/ajprenal.00080.2004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/21120
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Title
Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules
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Abstract
We investigated the regulation of organic anion transport driven by the organic anion transporter 3 (OAT3), a multispecific OAT localized at the basolateral membrane of the renal proximal tubule. PMA, a PKC activator, inhibited uptake of estrone sulfate (ES), a prototypic substrate for OAT3, in a dose- and time-dependent manner. This inhibition was reduced by 100 nM bisindoylmaleimide I (BIM), a specific PKC inhibitor. The α1- adrenergic receptor agonist phenylephrine also inhibited ES uptake, and this effect was reduced by BIM. These results suggest that PKC activation downregulates OAT3-mediated organic anion transport. In contrast, epidermal growth factor (EGF) increased ES uptake following activation of MAPK. Exposure to PGE2or dibutyryl (db)-cAMP also enhanced ES uptake. Stimulation produced by PGE2and db-cAMP was prevented by the PKA inhibitor H-89, indicating that this stimulation required PKA activation. In addition, inhibition of cyclooxygenase 1 (COX1) (but not COX2) inhibited ES uptake. Furthermore, the stimulatory effect of EGF was eliminated by inhibition of either COX1 or PKA. These data suggest that EGF stimulates ES uptake by a process in which MAPK activation results in increased PGE2production that, in turn, activates PKA and subsequently stimulates ES uptake. Interestingly, EGF did not induce upregulation immediately following phenylephrine-induced downregulation; and phenylephrine did not induce downregulation immediately after EGF-induced upregulation. These data are the first to show the regulatory response of organic anion transport driven by OAT3 in intact renal proximal tubules.