HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1599    most recent 00473.2006v1 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 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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Schneider, R. Articles by Gekle, M. Search for Related Content PubMed PubMed Citation Articles by Schneider, R. Articles by Gekle, M.

Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats

¹Institute of Physiology, ²Clinic of Internal Medicine I, Division of Nephrology, University of Wuerzburg, Wuerzburg, Germany

Submitted 30 November 2006 ; accepted in final form 19 January 2007

Ischemic acute renal failure (iARF) was described to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate-limiting step of renal organic anion secretion is its basolateral uptake into proximal tubular cells. This process is mediated by the organic anion transporters OAT1 and OAT3, which both have a broad spectrum of substrates including a variety of pharmaceutics and toxins. Using a rat model of iARF, we investigated whether impairing the secretion of the organic anion PAH might be associated with downregulation of OAT1 or OAT3. Inulin and PAH clearance was determined starting from 6 up to 336 h after ischemia-reperfusion (I/R) injury. Net secretion of PAH was calculated and OAT1 as well as OAT3 expression was analyzed by RT-PCR and Western blotting. Inulin and PAH clearance along with PAH net secretion were initially diminished after I/R injury with a gradual recovery during follow-up. This initial impairment after iARF was accompanied by decreased mRNA and protein levels of OAT1 and OAT3 in clamped animals compared with sham-operated controls. In correlation to the improvement of kidney function, both mRNA and protein levels of OAT1 and OAT3 were upregulated during the follow-up. Thus decreased expression of OAT1 and OAT3 is sufficient to explain the decline of PAH secretion after iARF. As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF.

organic anion transporter 1; organic anion transporter 3; proximal tubule; basolateral uptake; renal plasma flow; glomerular filtration; inulin; clearance; PAH net secretion

This article has been cited by other articles:

				S.-Y. Ahn and S. K. Nigam Toward a Systems Level Understanding of Organic Anion and Other Multispecific Drug Transporters: A Remote Sensing and Signaling Hypothesis Mol. Pharmacol., September 1, 2009; 76(3): 481 - 490. [Abstract] [Full Text] [PDF]

				M. Nakakariya, Y. Shima, Y. Shirasaka, K. Mitsuoka, T. Nakanishi, and I. Tamai Organic anion transporter OAT1 is involved in renal handling of citrulline Am J Physiol Renal Physiol, July 1, 2009; 297(1): F71 - F79. [Abstract] [Full Text] [PDF]

				O. Kwon, W.-W. Wang, and S. Miller Renal organic anion transporter 1 is maldistributed and diminishes in proximal tubule cells but increases in vasculature after ischemia and reperfusion Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1807 - F1816. [Abstract] [Full Text] [PDF]

				J. Roberts, B. Chen, L. M. Curtis, A. Agarwal, P. W. Sanders, and K. R. Zinn Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1408 - F1412. [Abstract] [Full Text] [PDF]