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Title: Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules
Authors: S. Soodvilai
V. Chatsudthipong
K. K. Evans
S. H. Wright
W. H. Dantzler
Mahidol University
University of Arizona
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Nov-2004
Citation: American Journal of Physiology - Renal Physiology. Vol.287, No.5 56-5 (2004)
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.
ISSN: 03636127
Appears in Collections:Scopus 2001-2005

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