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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/F1057    most recent 00185.2005v1 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 (4) Citing Articles via Google Scholar Google Scholar Articles by Soodvilai, S. Articles by Chatsudthipong, V. Search for Related Content PubMed PubMed Citation Articles by Soodvilai, S. Articles by Chatsudthipong, V.

Involvement of tyrosine kinase and PI3K in the regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules

¹Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; and ²Department of Physiology, University of Arizona, Tucson, Arizona

Submitted 4 May 2005 ; accepted in final form 8 June 2005

It was shown previously that OAT3 activity was differentially regulated by protein kinases including MAPK, PKA, and PKC. The present study investigated the short-term effect of tyrosine kinase and phosphatidylinositol 3-kinase (PI3K) on OAT3-mediated organic anion transport in S2 segments of renal proximal tubules. Genistein, a tyrosine kinase inhibitor, and wortmannin, a PI3K inhibitor, inhibited transport of estrone sulfate, a prototypic substrate for OAT3, in a dose-dependent manner. Previously, we showed that epidermal growth factor (EGF) stimulated OAT3 activity via the MAPK pathway. In the present study, we investigated whether EGF-stimulated OAT3 activity was dependent on tyrosine kinase and PI3K. We showed that EGF stimulation of OAT3 was reduced by inhibition of tyrosine kinase or PI3K, suggesting that they play a role in the stimulatory process. Inhibitory effects also indicated that tyrosine kinase and PI3K are involved in the MAPK pathway for EGF stimulation of OAT3 in intact renal proximal tubules, with PI3K acting upstream and tyrosine kinase acting downstream of mitogen-activated/extracellular signal-regulated kinase kinase activation.

kidney; MAPK; organic anion; EGF

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