QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted 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 (53) Citing Articles via Google Scholar Google Scholar Articles by Hollon, T. R. Articles by Sibley, D. R. Search for Related Content PubMed PubMed Citation Articles by Hollon, T. R. Articles by Sibley, D. R.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 15, 2002, 22(24):10801-10810

Mice Lacking D₅ Dopamine Receptors Have Increased Sympathetic Tone and Are Hypertensive

Tom R. Hollon^{1, *}, Martin J. Bek^{3, *}, Jean E. Lachowicz⁴, Marjorie A. Ariano⁵, Eva Mezey², Ramesh Ramachandran⁶, Scott R. Wersinger⁶, Patricio Soares-da-Silva⁷, Zhi Fang Liu¹, Alexander Grinberg⁸, John Drago⁸, W. Scott Young III⁶, Heiner Westphal⁸, Pedro A. Jose³, and David R. Sibley¹

¹ Molecular Neuropharmacology Section and ² Basic Neurosciences Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, ³ Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, ⁴ CNS/Cardiovascular Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, ⁵ Department of Neuroscience, The Chicago Medical School, North Chicago, Illinois 60064, ⁶ Section on Neural Gene Expression, National Institute of Mental Health, Bethesda, Maryland 20892, ⁷ Institute of Pharmacology and Therapeutics, Faculty of Medicine of Porto, Porto, Portugal, and ⁸ Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Dopamine is an important transmitter in the CNS and PNS, critically regulating numerous neuropsychiatric and physiological functions. These actions of dopamine are mediated by five distinct receptor subtypes. Of these receptors, probably the least understood in terms of physiological functions is the D₅ receptor subtype. To better understand the role of the D₅ dopamine receptor (DAR) in normal physiology and behavior, we have now used gene-targeting technology to create mice that lack this receptor subtype. We find that the D₅ receptor-deficient mice are viable and fertile and appear to develop normally. No compensatory alterations in other dopamine receptor subtypes were observed. We find, however, that the mutant mice develop hypertension and exhibit significantly elevated blood pressure (BP) by 3 months of age. This hypertension appears to be caused by increased sympathetic tone, primarily attributable to a CNS defect. Our data further suggest that this defect involves an oxytocin-dependent sensitization of V₁ vasopressin and non-NMDA glutamatergic receptor-mediated pathways, potentially within the medulla, leading to increased sympathetic outflow. These results indicate that D₅ dopamine receptors modulate neuronal pathways regulating blood pressure responses and may provide new insights into mechanisms for some forms of essential hypertension in humans, a disease that afflicts up to 25% of the aged adult population in industrialized societies.

Key words: D₅ receptor; gene knock-out; hypertension; sympathetic tone; oxytocin; vasopressin

---

^* T.R.H. and M.J.B. contributed equally to this work.

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/222410801-10$05.00/0

This article has been cited by other articles:

				F.-W. Zhou, Y. Jin, S. G. Matta, M. Xu, and F.-M. Zhou An Ultra-Short Dopamine Pathway Regulates Basal Ganglia Output J. Neurosci., August 19, 2009; 29(33): 10424 - 10435. [Abstract] [Full Text] [PDF]

				H.-H. Hsu, K. Duning, H. H. Meyer, M. Stolting, T. Weide, S. Kreusser, T. van Le, C. Gerard, R. Telgmann, S.-M. Brand-Herrmann, et al. Hypertension in mice lacking the CXCR3 chemokine receptor Am J Physiol Renal Physiol, April 1, 2009; 296(4): F780 - F789. [Abstract] [Full Text] [PDF]

				A. Sahu, K. R. Tyeryar, H. O. Vongtau, D. R. Sibley, and A. S. Undieh D5 Dopamine Receptors are Required for Dopaminergic Activation of Phospholipase C Mol. Pharmacol., March 1, 2009; 75(3): 447 - 453. [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]

				E. Argilli, D. R. Sibley, R. C. Malenka, P. M. England, and A. Bonci Mechanism and Time Course of Cocaine-Induced Long-Term Potentiation in the Ventral Tegmental Area J. Neurosci., September 10, 2008; 28(37): 9092 - 9100. [Abstract] [Full Text] [PDF]

				R. Howden, E. Liu, L. Miller-DeGraff, H. L. Keener, C. Walker, J. A. Clark, P. H. Myers, D. C. Rouse, T. Wiltshire, and S. R. Kleeberger The genetic contribution to heart rate and heart rate variability in quiescent mice Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H59 - H68. [Abstract] [Full Text] [PDF]

				C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]

				J. J. Gildea, X. Wang, P. A. Jose, and R. A. Felder Differential D1 and D5 Receptor Regulation and Degradation of the Angiotensin Type 1 Receptor Hypertension, February 1, 2008; 51(2): 360 - 366. [Abstract] [Full Text] [PDF]

				Z. Wang, I. Armando, L. D. Asico, C. Escano, X. Wang, Q. Lu, R. A. Felder, C. G. Schnackenberg, D. R. Sibley, G. M. Eisner, et al. The elevated blood pressure of human GRK4{gamma} A142V transgenic mice is not associated with increased ROS production Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2083 - H2092. [Abstract] [Full Text] [PDF]

				L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]

				M. J. Bek, X. Wang, L. D. Asico, J. E. Jones, S. Zheng, X. Li, G. M. Eisner, D. K. Grandy, R. M. Carey, P. Soares-da-Silva, et al. Angiotensin-II Type 1 Receptor-Mediated Hypertension in D4 Dopamine Receptor-Deficient Mice Hypertension, February 1, 2006; 47(2): 288 - 295. [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]

				C. J. Zeiss Neuroanatomical Phenotyping in the Mouse: The Dopaminergic System Veterinary Pathology, November 1, 2005; 42(6): 753 - 773. [Abstract] [Full Text] [PDF]

				M. Sjoquist, S.-L. Lee, and P. Hansell CNS-induced natriuresis, neurohypophyseal peptides and renal dopamine and noradrenaline excretion in prehypertensive salt-sensitive Dahl rats Exp Physiol, November 1, 2005; 90(6): 847 - 853. [Abstract] [Full Text] [PDF]

				C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [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]

				Z. Yang, L. D. Asico, P. Yu, Z. Wang, J. E. Jones, R.-k. Bai, D. R. Sibley, R. A. Felder, and P. A. Jose D5 dopamine receptor regulation of phospholipase D Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H55 - H61. [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]

				M. Kobayashi, C. Iaccarino, A. Saiardi, V. Heidt, Y. Bozzi, R. Picetti, C. Vitale, H. Westphal, J. Drago, and E. Borrelli Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice PNAS, August 3, 2004; 101(31): 11465 - 11470. [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]

				C. Zeng, Y. Luo, L. D. Asico, U. Hopfer, G. M. Eisner, R. A. Felder, and P. A. Jose Perturbation of D1 Dopamine and AT1 Receptor Interaction in Spontaneously Hypertensive Rats Hypertension, October 1, 2003; 42(4): 787 - 792. [Abstract] [Full Text] [PDF]

				D. Centonze, C. Grande, E. Saulle, A. B. Martin, P. Gubellini, N. Pavon, A. Pisani, G. Bernardi, R. Moratalla, and P. Calabresi Distinct Roles of D1 and D5 Dopamine Receptors in Motor Activity and Striatal Synaptic Plasticity J. Neurosci., September 17, 2003; 23(24): 8506 - 8512. [Abstract] [Full Text] [PDF]

				D. Centonze, C. Grande, A. Usiello, P. Gubellini, E. Erbs, A. B. Martin, A. Pisani, N. Tognazzi, G. Bernardi, R. Moratalla, et al. Receptor Subtypes Involved in the Presynaptic and Postsynaptic Actions of Dopamine on Striatal Interneurons J. Neurosci., July 16, 2003; 23(15): 6245 - 6254. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help