AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 282: F458-F464, 2002; doi:10.1152/ajprenal.00173.2001
0363-6127/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
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 ISI Web of Science (21)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Notenboom, S.
Right arrow Articles by Masereeuw, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Notenboom, S.
Right arrow Articles by Masereeuw, R.
Vol. 282, Issue 3, F458-F464, March 2002

Role of NO in endothelin-regulated drug transport in the renal proximal tubule

Sylvia Notenboom1,3, David S. Miller2,3, Paul Smits1, Frans G. M. Russel1, and Rosalinde Masereeuw1

1 Department of Pharmacology and Toxicology, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands; 2 Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, North Carolina 27709; and 3 Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672

We previously demonstrated in intact killifish renal proximal tubules that endothelin (ET), acting through an ETB receptor and protein kinase C (PKC), reduced transport mediated by multidrug resistance-associated protein 2 (Mrp2), i.e., luminal accumulation of fluorescein methotrexate (FL-MTX) (Masereeuw R, Terlouw SA, Van Aubel RAMH, Russel FGM, and Miller DS. Mol Pharmacol 57: 59-67, 2000). In the present study, we used confocal microscopy and quantitative image analysis to measure Mrp2-mediated transport of FL-MTX in killifish tubules as an indicator of the status of this ET-fired, intracellular signaling pathway. Exposing tubules to sodium nitroprusside (SNP), a nitric oxide (NO) donor, signaled a reduction in luminal accumulation of FL-MTX, which suggested pathway activation. NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, blocked the action of ET-1 on transport. Because SNP effects on transport were blocked by bisindoylmaleide, a PKC-selective inhibitor, but not by RES-701-1, an ETB-receptor antagonist, generation of NO occurred after ETB receptor signaling but before PKC activation. NO generation was implicated in the actions of several nephrotoxicants, i.e., diatrizoate, gentamicin, amikacin, HgCl2, and CdCl2, each of which decreased Mrp2-mediated transport by activating ET signaling. For each nephrotoxicant, decreased FL-MTX transport was prevented when tubules were exposed to L-NMMA. ET-1 and each nephrotoxicant stimulated NO production by the tubules, as determined by a fluorescence-based assay. Together, the data show that NO generation follows ET binding to the basolateral ETB receptor and that, in activating the ET-signaling pathway, nephrotoxicants produce NO, a molecule that could contribute to subsequent toxic effects.

multidrug resistance-associated protein 2; calcium; endothelin signaling; protein kinase C; xenobiotic transport; nitric oxide


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
V. Reichel, R. Masereeuw, J. J. M. W. van den Heuvel, D. S. Miller, and G. Fricker
Transport of a fluorescent cAMP analog in teleost proximal tubules
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2382 - R2389.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Goddard, N. R. Johnston, A. D. Cumming, and D. J. Webb
Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade
Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1433 - F1438.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. E. Wever, R. Masereeuw, D. S. Miller, X. M. Hang, and G. Flik
Endothelin and calciotropic hormones share regulatory pathways in multidrug resistance protein 2-mediated transport
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F38 - F46.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
C. Zeng, U. Hopfer, L. D. Asico, G. M. Eisner, R. A. Felder, and P. A. Jose
Altered AT1 Receptor Regulation of ETB Receptors in Renal Proximal Tubule Cells of Spontaneously Hypertensive Rats
Hypertension, October 1, 2005; 46(4): 926 - 931.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
B. Bauer, A. M. S. Hartz, G. Fricker, and D. S. Miller
Modulation of p-Glycoprotein Transport Function at the Blood-Brain Barrier
Experimental Biology and Medicine, February 1, 2005; 230(2): 118 - 127.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. H. Wright and W. H. Dantzler
Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport
Physiol Rev, July 1, 2004; 84(3): 987 - 1049.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. Notenboom, D. S. Miller, P. Smits, F. G. M. Russel, and R. Masereeuw
Involvement of guanylyl cyclase and cGMP in the regulation of Mrp2-mediated transport in the proximal tubule
Am J Physiol Renal Physiol, July 1, 2004; 287(1): F33 - F38.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. A. Terlouw, C. Graeff, P. H. E. Smeets, G. Fricker, F. G. M. Russel, R. Masereeuw, and D. S. Miller
Short- and Long-Term Influences of Heavy Metals on Anionic Drug Efflux from Renal Proximal Tubule
J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 578 - 585.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online