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: 293/5/R1809    most recent 00293.2007v1 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 ISI 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 ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Govindarajan, R. Articles by Unadkat, J. D. Search for Related Content PubMed PubMed Citation Articles by Govindarajan, R. Articles by Unadkat, J. D.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta

Departments of ¹Pharmaceutics, ²Biology, and ³Pathology, University of Washington, Seattle, Washington; ⁴Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona and Centro de Investigacíon, Biomédica en Red-Enfermedades Hepáticasay Digestivas, Barcelona, Spain; and ⁵Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine and ⁶Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland

Submitted 27 April 2007 ; accepted in final form 24 August 2007

To better understand the role of human equilibrative (hENTs) and concentrative (hCNTs) nucleoside transporters in physiology and pharmacology, we investigated the regional, cellular, and spatial distribution of two hCNTs (hCNT1 and hCNT2) and two hENTs (hENT1 and hENT2) in four human tissues. Using in situ hybridization and immunohistochemical techniques, we found that the duodenum expressed hCNT1 and hCNT2 mRNAs in enterocytes and hENT1 and hENT2 mRNAs in crypt cells. In these cells, the hCNT and hENT proteins were predominantly localized in the apical and lateral membrane, respectively. Hepatocytes expressed higher levels of mRNAs of hENT1, hCNT1, and hENT2 than of hCNT2 and expressed all these proteins at hepatocyte cell borders and in the cytoplasm. While the kidney expressed hCNT1 and hCNT2 mRNAs in the proximal tubules, hENT1 and hENT2 mRNAs were present in the distal tubules, glomeruli, endothelial cells, and vascular smooth muscle cells. Proximal tubules adjacent to corticomedullary junctions expressed hENT1, hCNT1, and hCNT2 mRNA. Immunolocalization studies revealed predominant localization of hCNTs in the brush-border membrane of the proximal tubular epithelial cells and hENTs in the basolateral membrane of the distal tubular epithelial cells. Chorionic villi sections of human term placenta expressed mRNAs and proteins for hENT1 and hENT2 but only mRNA for hCNT2. Immunolocalization studies showed presence of hENT1 in the brush-border membrane of the syncytiotrophoblasts. These data are critical for a better understanding of the role of nucleoside transporters in the physiological and pharmacological effects of nucleosides and nucleoside drugs, respectively.

expression; localization; human tissue

This article has been cited by other articles:

				R. Govindarajan, C. J. Endres, D. Whittington, E. LeCluyse, M. Pastor-Anglada, C.-M. Tse, and J. D. Unadkat Expression and hepatobiliary transport characteristics of the concentrative and equilibrative nucleoside transporters in sandwich-cultured human hepatocytes Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G570 - G580. [Abstract] [Full Text] [PDF]

				S. A. Veltkamp, D. Pluim, O. van Tellingen, J. H. Beijnen, and J. H. M. Schellens Extensive Metabolism and Hepatic Accumulation of Gemcitabine After Multiple Oral and Intravenous Administration in Mice Drug Metab. Dispos., August 1, 2008; 36(8): 1606 - 1615. [Abstract] [Full Text] [PDF]

				S. A. Veltkamp, D. Pluim, M. A.J. van Eijndhoven, M. J. Bolijn, F. H.G. Ong, R. Govindarajan, J. D. Unadkat, J. H. Beijnen, and J. H.M. Schellens New insights into the pharmacology and cytotoxicity of gemcitabine and 2',2'-difluorodeoxyuridine Mol. Cancer Ther., August 1, 2008; 7(8): 2415 - 2425. [Abstract] [Full Text] [PDF]

				A. Kulick, C. Panico, P. Gill, and W. J. Welch Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule Am J Physiol Renal Physiol, July 1, 2008; 295(1): F37 - F41. [Abstract] [Full Text] [PDF]

				H. Castrop Modulation of adenosine receptor expression in the proximal tubule: a novel adaptive mechanism to regulate renal salt and water metabolism Am J Physiol Renal Physiol, July 1, 2008; 295(1): F35 - F36. [Full Text] [PDF]