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: 291/5/F945    most recent 00111.2006v1 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 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 Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Fardoun, R. Z. Articles by Lokhandwala, M. Search for Related Content PubMed PubMed Citation Articles by Fardoun, R. Z. Articles by Lokhandwala, M.

TRANSLATIONAL PHYSIOLOGY

Role of oxidative stress in defective renal dopamine D1 receptor-G protein coupling and function in old Fischer 344 rats

Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Texas

Submitted 10 April 2006 ; accepted in final form 30 May 2006

Aging is associated with an increase in oxidative stress. Previously, we have reported that dopamine failed to inhibit proximal tubular Na-K-ATPase and to promote sodium excretion in old rats (Beheray S, Kansra V, Hussain T, and Lokhandwala MF. Kidney Int 58: 712–720, 2000). This was due to uncoupling of dopamine D1 receptors from G proteins resulting from hyperphosphorylation of D1 receptors. The present study was designed to test the role of oxidative stress in the age-related decline in renal dopamine D1 receptor function. We observed that old animals had increased malondialdehyde (MDA) levels, a biomarker of oxidative stress, and decreased D1 receptor number and protein in the proximal tubules (PT) compared with adult rats. In old rats, there was increased G protein-coupled receptor kinase-2 (GRK-2) abundance, increased basal serine phosphorylation of D1 receptors, and defective D1 receptor-G protein coupling in PT membranes. Interestingly, supplementation with an antioxidant, tempol (1 mmol/l in drinking water for 15 days), lowered MDA levels and normalized D1 receptor number and protein in old rats to the level seen in adult rats. Furthermore, tempol decreased GRK-2 abundance and D1 receptor serine phosphorylation and restored D1 receptor-G protein coupling in PT of old rats. The functional consequence of these changes was the restoration of the natriuretic response to D1 receptor activation in tempol-supplemented old rats. Therefore, in old rats, tempol reduces oxidative stress and prevents GRK-2 membranous abundance and hyperphosphorylation of D1 receptors, resulting in restoration of D1 receptor-G protein coupling and the natriuretic response to SKF-38393. Thus tempol, by lowering oxidative stress, normalizes the age-related decline in dopamine receptor function.

G protein receptor kinases; antioxidant; tempol; SKF-38393

This article has been cited by other articles:

				L. George, M. F. Lokhandwala, and M. Asghar Exercise activates redox-sensitive transcription factors and restores renal D1 receptor function in old rats Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1174 - F1180. [Abstract] [Full Text] [PDF]

				C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]

				M. Asghar, A. Chillar, and M. F. Lokhandwala Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1326 - C1331. [Abstract] [Full Text] [PDF]

				C. Zeng, V. A. M. Villar, G. M. Eisner, S. M. Williams, R. A. Felder, and P. A. Jose G Protein-Coupled Receptor Kinase 4: Role in Blood Pressure Regulation Hypertension, June 1, 2008; 51(6): 1449 - 1455. [Full Text] [PDF]

				M. Asghar, L. George, and M. F. Lokhandwala Exercise decreases oxidative stress and inflammation and restores renal dopamine D1 receptor function in old rats Am J Physiol Renal Physiol, September 1, 2007; 293(3): F914 - F919. [Abstract] [Full Text] [PDF]

				A. A. Banday and M. F. Lokhandwala Oxidative stress reduces renal dopamine D1 receptor-Gq/11{alpha} G protein-phospholipase C signaling involving G protein-coupled receptor kinase 2 Am J Physiol Renal Physiol, July 1, 2007; 293(1): F306 - F315. [Abstract] [Full Text] [PDF]

				A. A. Banday, F. R. Fazili, and M. F. Lokhandwala Oxidative Stress Causes Renal Dopamine D1 Receptor Dysfunction and Hypertension via Mechanisms That Involve Nuclear Factor-{kappa}B and Protein Kinase C J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1446 - 1457. [Abstract] [Full Text] [PDF]