This Article Full Text Full Text (PDF) 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carey, R. M. Search for Related Content PubMed PubMed Citation Articles by Carey, R. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DOPAMINE SODIUM Related Collections Animal models of human disease Cell signalling/signal transduction Other hypertension Gene expression Hypertension - basic studies

(Hypertension. 2001;38:297.)
© 2001 American Heart Association, Inc.

Theodore Cooper Memorial Lecture

Renal Dopamine System

Paracrine Regulator of Sodium Homeostasis and Blood Pressure

Robert M. Carey

Department of Medicine, University of Virginia School of Medicine, Charlottesville.

Correspondence to Dr Robert M. Carey, Box 800793, University of Virginia Health System, Charlottesville, VA 22908-0793.

Abstract

Abstract—— All of the components of a complete dopamine system are present within the kidney, where dopamine acts as a paracrine substance in the control of sodium excretion. Dopamine receptors can be divided into D₁-like (D₁ and D₅) receptors that stimulate adenylyl cyclase and D₂-like (D₂, D₃, and D₄) receptors that inhibit adenylyl cyclase. All 5 receptor subtypes are expressed in the kidney, albeit in low copy. Dopamine is synthesized extraneuronally in proximal tubule cells, exported from these cells largely into the tubule lumen, and interacts with D₁-like receptors to inhibit the Na⁺-H⁺ exchanger and Na⁺,K⁺-ATPase, decreasing tubule sodium reabsorption. During moderate sodium surfeit, dopamine tone at D₁-like receptors accounts for 50% of sodium excretion. In experimental and human hypertension, 2 renal dopaminergic defects have been described: (1) decreased renal generation of dopamine and (2) a D₁ receptor-G protein coupling defect. Both defects lead to renal sodium retention, and each may play an important role in the pathophysiology of essential hypertension.

Key Words: receptors, dopamine • sodium excretion • blood pressure • cell signaling

This article has been cited by other articles:

				C. S. Escano, I. Armando, X. Wang, L. D. Asico, A. Pascua, Y. Yang, Z. Wang, Y.-S. Lau, and P. A. Jose Renal dopaminergic defect in C57Bl/6J mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1660 - R1669. [Abstract] [Full Text] [PDF]

				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]

				B. Yao, R. C. Harris, and M.-Z. Zhang Intrarenal Dopamine Attenuates Deoxycorticosterone Acetate/High Salt-Induced Blood Pressure Elevation in Part Through Activation of a Medullary Cyclooxygenase 2 Pathway Hypertension, November 1, 2009; 54(5): 1077 - 1083. [Abstract] [Full Text] [PDF]

				M.-Z. Zhang, B. Yao, X. Fang, S. Wang, J. P. Smith, and R. C. Harris Intrarenal Dopaminergic System Regulates Renin Expression Hypertension, March 1, 2009; 53(3): 564 - 570. [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]

				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. Maurel, O. Spreux-Varoquaux, F. Amenta, S. K. Tayebati, D. Tomassoni, M.-H. Seguelas, A. Parini, and N. Pizzinat Vesicular monoamine transporter 1 mediates dopamine secretion in rat proximal tubular cells Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1592 - F1598. [Abstract] [Full Text] [PDF]

				C. Kirchheimer, C. F. Mendez, A. Acquier, and S. Nowicki Role of 20-HETE in D1/D2 dopamine receptor synergism resulting in the inhibition of Na+-K+-ATPase activity in the proximal tubule Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1435 - F1442. [Abstract] [Full Text] [PDF]

				M. J. Pinho, M. P. Serrao, and P. Soares-da-Silva High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1452 - F1463. [Abstract] [Full Text] [PDF]

				L. J. Salomone, N. L. Howell, H. E. McGrath, B. A. Kemp, S. R. Keller, J. J. Gildea, R. A. Felder, and R. M. Carey Intrarenal Dopamine D1-Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism Hypertension, January 1, 2007; 49(1): 155 - 161. [Abstract] [Full Text] [PDF]

				Z. Yang, L. D. Asico, P. Yu, Z. Wang, J. E. Jones, C. S. Escano, X. Wang, M. T. Quinn, D. R. Sibley, G. G. Romero, et al. D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R96 - R104. [Abstract] [Full Text] [PDF]

				A. M. Bertorello and J. I. Sznajder The Dopamine Paradox in Lung and Kidney Epithelia: Sharing the Same Target but Operating Different Signaling Networks Am. J. Respir. Cell Mol. Biol., November 1, 2005; 33(5): 432 - 437. [Abstract] [Full Text] [PDF]

				M.-Z. Zhang, B. Yao, J. A. McKanna, and R. C. Harris Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems Am J Physiol Renal Physiol, April 1, 2005; 288(4): F840 - F845. [Abstract] [Full Text] [PDF]

				C. Zeng, Z. Yang, Z. Wang, J. Jones, X. Wang, J. Altea, A. J. Mangrum, U. Hopfer, D. R. Sibley, G. M. Eisner, et al. Interaction of Angiotensin II Type 1 and D5 Dopamine Receptors in Renal Proximal Tubule Cells Hypertension, April 1, 2005; 45(4): 804 - 810. [Abstract] [Full Text] [PDF]

				M. R. Garrett, H. Meng, J. P. Rapp, and B. Joe Locating a Blood Pressure Quantitative Trait Locus Within 117 kb on the Rat Genome: Substitution Mapping and Renal Expression Analysis Hypertension, March 1, 2005; 45(3): 451 - 459. [Abstract] [Full Text] [PDF]

				A. Nurnberger, M. Rabiger, A. Mack, J. Diaz, P. Sokoloff, B. Muhlbauer, and G. Luippold Subapical Localization of the Dopamine D3 Receptor in Proximal Tubules of the Rat Kidney J. Histochem. Cytochem., December 1, 2004; 52(12): 1647 - 1655. [Abstract] [Full Text] [PDF]

				C. Zeng, H. Sanada, H. Watanabe, G. M. Eisner, R. A. Felder, and P. A. Jose Functional genomics of the dopaminergic system in hypertension Physiol Genomics, November 17, 2004; 19(3): 233 - 246. [Abstract] [Full Text] [PDF]

				K. J. Pettersson-Fernholm, C. M. Forsblom, M. Perola, J. A. Fagerudd, and P.-H. Groop Dopamine D3 receptor gene polymorphisms, blood pressure and nephropathy in type 1 diabetic patients Nephrol. Dial. Transplant., June 1, 2004; 19(6): 1432 - 1436. [Abstract] [Full Text] [PDF]

				J. M. Stern, J. Chen, R. B. Silver, D. P. Poppas, E. D. Vaughan Jr., and D. Felsen Effect of UUO on D1aR expression reveals a link among dopamine, transforming growth factor-{beta}, and nitric oxide Am J Physiol Renal Physiol, March 1, 2004; 286(3): F509 - F515. [Abstract] [Full Text]

				H. Mayan, X.-P. Ni, S. Almog, and M. H. Humphreys Suppression of {gamma}-Melanocyte-Stimulating Hormone Secretion Is Accompanied by Salt-Sensitive Hypertension in the Rat Hypertension, November 1, 2003; 42(5): 962 - 967. [Abstract] [Full Text] [PDF]

				S. Noori, P. Friedlich, and I. Seri Pharmacology Review: Developmentally Regulated Cardiovascular, Renal, and Neuroendocrine Effects of Dopamine NeoReviews, October 1, 2003; 4(10): e283 - 288. [Full Text] [PDF]

				R. Efendiev, C. E. Budu, A. R. Cinelli, A. M. Bertorello, and C. H. Pedemonte Intracellular Na+ Regulates Dopamine and Angiotensin II Receptors Availability at the Plasma Membrane and Their Cellular Responses in Renal Epithelia J. Biol. Chem., August 1, 2003; 278(31): 28719 - 28726. [Abstract] [Full Text] [PDF]

				P. Bianchi, M.-H. Seguelas, A. Parini, and C. Cambon Activation of Pro-Apoptotic Cascade by Dopamine in Renal Epithelial Cells is Fully Dependent on Hydrogen Peroxide Generation by Monoamine Oxidases J. Am. Soc. Nephrol., April 1, 2003; 14(4): 855 - 862. [Abstract] [Full Text] [PDF]