Submitted on January 25, 2007
Accepted on February 23, 2007
ROLE OF MAPK AND PKA IN REGULATION OF rbOCT2-MEDIATED RENAL ORGANIC CATION TRANSPORT
Sunhapas Soodvilai1, Atip Chatsudthipong2, and Varanuj Chatsudthipong2*
1 Faculty of Pharmaceutical Sciences, Ubon Ratchathanee University, Ubon Ratchathani, Thailand
2 Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
* To whom correspondence should be addressed. E-mail: scvcs{at}mahidol.ac.th.
The effects of protein kinases, MAPK and PKA, on the regulation of OCT2 were investigated both in a heterologous cell system (CHO-K1 cells stably transfected with rbOCT2) 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.
