Altered renal expression of relevant clinical drug transporters in different models of acute uremia in rats. Role of urea levels
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2015-06-09
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Editor
Karger
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Descripción
Background/Aims: Organic anion transporter 1 (Oat1) and 3 (Oat3) are organic anion
transporters that play critical roles in the body disposition of numerous clinically important
drugs. We investigated the effects of acute uremia on the renal expression of Oat1 and Oat3
in three in vivo experimental models of acute kidney injury (AKI): induced by ischemia, by
ureteral obstruction and by the administration of HgCl2
. We also evaluated the influence of
urea in the expression of these transporters in proximal tubular cells suspensions. Methods:
Membranes were isolated from kidneys of each experimental group and from cell suspensions
incubated with different urea concentrations. Oat1 and Oat3 expressions were performed by
immunoblotting. Results: A good correlation between uremia and the renal protein expression
of Oat1 and Oat3 was observed in vivo. Moreover, the incubation of isolated proximal tubular
cells with different concentrations of urea decreases protein expression of Oat1 and Oat3 in
plasma membranes in a dose-dependent manner. Conclusion: The more severe the renal
failure, the more important is the decrease in protein expression of the transporters in renal
membranes where they are functional. The in vitro study demonstrates that urea accounts,
at least in part, for the decreased expression of Oat1 and Oat3 in proximal tubule plasma
membranes.
Palabras clave
Uremic Toxins, Organic Anion Transport Protein 1, Organic Anion Transport Protein 3, Acute Kidney Injury