Submitted on March 16, 2008
Accepted on October 8, 2008
Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis
Yu-Mi Kim1*, Wan Young Kim2, Hyun-Wook Lee3, Jin Kim3, H. Moo Kwon4, Janet D Klein5, Jeff M Sands6, and Dongun Kim7
1 Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of
2 Anatomy, The Catholic Univeristy of Korea, Seoul, Korea, Republic of; Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of
3 Anatomy, The Catholic University of Korea, Seoul, Korea, Republic of; Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of
4 Medicine, University of Maryland, Baltimore, Maryland, United States
5 Medicine, Renal Division, Emory University, Atlanta, Georgia, United States
6 Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
7 Pediatrics, The Catholic University of Korea, Uijeongbu, Korea, Republic of
* To whom correspondence should be addressed. E-mail: ego_amo_te{at}hanmail.net.
In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study are to examine: 1) whether the inner medullary interstitial tonicity changes with different urine urea concentrations during osmotic dieresis; and 2) whether the same result occurs even if total urinary solute is decreased. Rats were fed a 4% high salt diet (HSD) or a 5% high urea diet (HUD) for 2 weeks and compared with the control rats fed regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and TonEBP transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low protein diet (LPD) or a 0.4% low salt diet (LSD) to decrease total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3 and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.
