JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Han, Y.-H.
Right arrow Articles by Pritchard, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Han, Y.-H.
Right arrow Articles by Pritchard, J. B.

Vol. 296, Issue 2, 450-457, February 2001

Characterization of a Novel Cationic Drug Transporter in Human Retinal Pigment Epithelial Cells

Yong-Hae Han, Douglas H. Sweet, Dan-Ning Hu and John B. Pritchard

Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (Y.-H.H, D.H.S., J.B.P.); and New York Medical College, The New York Eye and Ear Infirmary, New York, New York (D.-N.H.)

Retinal pigment epithelial (RPE) cells transport a variety of solutes, but the capacity of human RPE cells to transport drugs and xenobiotics is not well understood. As an initial step to address this issue, we have examined human RPE transport of verapamil. Transport of [3H]verapamil was measured in two human RPE cell lines (RPE/Hu and ARPE-19) grown to confluence on 12-well culture plates. Verapamil uptake by RPE/Hu cells was highly concentrative, reaching cell-to-medium ratios as high as 42 by 1 h. Uptake was saturable, with an apparent Km of 7.2 µM. Verapamil uptake decreased in the presence of metabolic inhibitors, low temperature, and organic cations, including quinidine, pyrilamine, quinacrine, and diphenhydramine. However, other organic cations, including tetraethylammonium and cimetidine failed to inhibit. Verapamil uptake was also inhibited by the cationic antiglaucoma drugs diltiazem, timolol, and propranolol. Verapamil uptake was insensitive to changes in membrane potential. However, transport was markedly altered by changes in pH. Decreasing external pH inhibited uptake, whereas efflux was stimulated. Intracellular acidification via NH4Cl prepulse also stimulated uptake. Identical findings were obtained using the commercially available cell line ARPE-19. In view of its unique specificity, the RPE cell verapamil transporter described above is a novel, heretofore undescribed, organic cation transporter, distinct from the known members of the OCT family of organic cation transporters.

0022-3565/01/2962-0450$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by U.S. Government


This article has been cited by other articles:


Home page
 IOVSHome page
N. Zhang, R. Kannan, C. T. Okamoto, S. J. Ryan, V. H. L. Lee, and D. R. Hinton
Characterization of Brimonidine Transport in Retinal Pigment Epithelium
Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 287 - 294.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
N. Ishiguro, T. Nozawa, A. Tsujihata, A. Saito, W. Kishimoto, K. Yokoyama, T. Yotsumoto, K. Sakai, T. Igarashi, and I. Tamai
INFLUX AND EFFLUX TRANSPORT OF H1-ANTAGONIST EPINASTINE ACROSS THE BLOOD-BRAIN BARRIER
Drug Metab. Dispos., May 1, 2004; 32(5): 519 - 524.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S.-J. Sheu and S.-N. Wu
Mechanism of Inhibitory Actions of Oxidizing Agents on Calcium-Activated Potassium Current in Cultured Pigment Epithelial Cells of the Human Retina
Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1237 - 1244.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. B. Goralski, G. Lou, M. T. Prowse, V. Gorboulev, C. Volk, H. Koepsell, and D. S. Sitar
The Cation Transporters rOCT1 and rOCT2 Interact with Bicarbonate but Play Only a Minor Role for Amantadine Uptake into Rat Renal Proximal Tubules
J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 959 - 968.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. H. Sweet, D. S. Miller, J. B. Pritchard, Y. Fujiwara, D. R. Beier, and S. K. Nigam
Impaired Organic Anion Transport in Kidney and Choroid Plexus of Organic Anion Transporter 3 (Oat3 (Slc22a8)) Knockout Mice
J. Biol. Chem., July 19, 2002; 277(30): 26934 - 26943.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
E. Cova, U. Laforenza, G. Gastaldi, Y. Sambuy, S. Tritto, A. Faelli, and U. Ventura
Guanidine Transport across the Apical and Basolateral Membranes of Human Intestinal Caco-2 Cells Is Mediated by Two Different Mechanisms
J. Nutr., July 1, 2002; 132(7): 1995 - 2003.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. Gao, A. Wenzel, C. Grimm, S. R. Vavricka, D. Benke, P. J. Meier, and C. E. Reme
Localization of Organic Anion Transport Protein 2 in the Apical Region of Rat Retinal Pigment Epithelium
Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 510 - 514.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.