role of p-glycoprotein expression and function in cystinotic renal proximal tubular cells22表达式和函数在cystinotic肾近端小管细胞.pdfVIP

Pharmaceutics 2011, 3, 782-792; doi:10.3390/pharmaceutics3040782 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Article Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells 1 2 1 3 Karen Peeters , Martijn J. Wilmer , Joost P. Schoeber , Dorien Reijnders , Lambertus P. van den Heuvel 1,3, Rosalinde Masereeuw 2 and Elena Levtchenko 1,* 1 Pediatric Nephrology, Katholieke Universiteit Leuven, Herestraat 49 Box 817, Leuven, Belgium 2 Department of Pharmacology and Toxicology (149), Radboud University Nijmegen Medical Center, Geert Grooteplein Noord 21, 6525 GA, Nijmegen, The Netherlands 3 Department of Pediatrics, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands * Author to whom correspondence should be addressed; E-Mail: elena.levtchenko@uzleuven.be; Tel.: +32-(0)16-341362; Fax: +32-(0)16-343842 Received: 22 September 2011; in revised form: 11 October 2011 / Accepted: 20 October 2011 / Published: 27 October 2011 Abstract: P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal tubular dysfunction similar to the phenotype of patients with cystinosis, an autosomal recessi