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Am J Physiol Renal Physiol 293: F21-F27, 2007. First published February 27, 2007; doi:10.1152/ajprenal.00043.2007
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EDITORIAL FOCUS

Role of MAPK and PKA in regulation of rbOCT2-mediated renal organic cation transport

Sunhapas Soodvilai,1,2 Atip Chatsudthipong,2 and Varanuj Chatsudthipong2

1Faculty of Pharmaceutical Sciences, Ubon Rajathanee University, Ubon Ratchathani, and 2Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand

Submitted 25 January 2007 ; accepted in final form 23 February 2007

The effects of protein kinases MAPK and PKA on the regulation of organic cation transporter 2 (OCT2) were investigated both in a heterologous cell system [Chinese hamster ovary (CHO-K1) cells stably transfected with rabbit (rb)OCT2] and in native intact rabbit renal proximal S2 segments. Inhibition of MEK (by U-0126) or PKA (by H-89) reduced transport activity of rbOCT2 in CHO-K1 cells. The inhibitory effect of U-0126 combined with H-89 produced no additive effect, indicating that the action of PKA and MAPK in the regulation of rbOCT2 is in a common pathway. Activation of PKA by forskolin stimulated rbOCT2 activity, and this stimulatory effect was eliminated by H-89, indicating that the stimulation required PKA activation. In S2 segments of rabbit renal proximal tubules, activation of MAPK (by EGF) and PKA (by forskolin) stimulated activity of rbOCT2, and this activation was abolished by U-0126 and H-89, respectively. This is the first study to show that MAPK and PKA are involved, apparently in a common pathway, in the regulation of OCT2 activity in both a heterologous cell system and intact renal proximal tubules.

kidney; proximal tubule; epidermal growth factor; H-89; tetraethylammonium


Address for reprint requests and other correspondence: V. Chatsudthipong, Dept. of Physiology, Faculty of Science, Mahidol Univ., Bangkok, Thailand 10400 (e-mail: scvcs{at}mahidol.ac.th)






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