| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RENAL AND ENDOCRINE |
al Pastor-Anglada1,2,3
1 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia
2 Institut de Biomedicina (IBUB)
3 CIBER Hepad, Universitat de Barcelona, Barcelona, Spain
We examined the role of the concentrative nucleoside transporter CNT3 in the establishment of a transepithelial flux of natural nucleosides and their pharmacologically active derivatives in renal epithelial cell lines. Murine PCT cells grown on a transwell dish showed endogenous CNT3 activity at their apical membrane that was responsible for the sodium-dependent transepithelial flux of both purine and pyrimidine nucleosides. hCNT3 was also identified in human kidney and its role in the transport of nucleosides was tested. To this end, MDCK cells, lacking endogenous CNT3 activity, were genetically engineered to express the human orthologue of CNT3 (hCNT3-MDCK cells). In these cells, hCNT3 was inserted into the apical membrane, thus generating, as for PCT cells, a transepithelial flux of both nucleosides and nucleoside-derived drugs. Apical-to-basolateral transepithelial flux was present in all cells expressing a functional CNT3 transporter and was significantly higher than that found either in PCT cells in absence of sodium or in mock-transfected MDCK cells. Nevertheless in all cases a significant amount of the transported nucleoside was retained and transformed inside cells. However release to the opposite compartment was CNT3 dependent, not only in terms of absolute flux (much higher when an apical CNT3 transporter was active) but also regarding metabolic transformations of the apically absorbed nucleosides. These results underline a critical role of CNT3 in the renal reabsorption of nucleosides and their derivatives as well as in their intracellular metabolism.
(Received 8 February 2007;
accepted after revision 2 April 2007;
first published online 5 April 2007)
Corresponding author F. Javier Casado: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda Diagonal 645, Edifici annex, Planta-1, E-08028 Barcelona, Spain. Email: fcasado{at}ub.edu
This article has been cited by other articles:
|
|
 |
|
  J. B. Rose and I. R. Coe Physiology of Nucleoside Transporters: Back to the Future. . . . Physiology, February 1, 2008; 23(1): 41 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Minuesa, S. Purcet, I. Erkizia, M. Molina-Arcas, M. Bofill, N. Izquierdo-Useros, F. J. Casado, B. Clotet, M. Pastor-Anglada, and J. Martinez-Picado Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 558 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Errasti-Murugarren, P. Cano-Soldado, M. Pastor-Anglada, and F. J. Casado Functional Characterization of a Nucleoside-Derived Drug Transporter Variant (hCNT3C602R) Showing Altered Sodium-Binding Capacity Mol. Pharmacol., February 1, 2008; 73(2): 379 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Govindarajan, A. H. Bakken, K. L. Hudkins, Y. Lai, F. J. Casado, M. Pastor-Anglada, C.-M. Tse, J. Hayashi, and J. D. Unadkat In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1809 - R1822. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
