The dopaminergic system in hypertension

2007 ◽  
Vol 112 (12) ◽  
pp. 583-597 ◽  
Author(s):  
Chunyu Zeng ◽  
Meng Zhang ◽  
Laureano D. Asico ◽  
Gilbert M. Eisner ◽  
Pedro A. Jose
Keyword(s):  
Blood Pressure ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Epithelial Transport ◽  
Receptor Subtypes ◽  
Smooth Muscle Contractility ◽  
Dopamine Receptor Subtypes ◽  
Sympathetic Nervous Systems ◽  
The Relationship ◽  
Regulation Of Blood Pressure

Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport, vascular smooth muscle contractility and production of reactive oxygen species and by interacting with the renin–angiotensin and sympathetic nervous systems. Dopamine receptors are classified into D1-like (D1 and D5) and D2-like (D2, D3 and D4) subtypes based on their structure and pharmacology. Each of the dopamine receptor subtypes participates in the regulation of blood pressure by mechanisms specific for the subtype. Some receptors regulate blood pressure by influencing the central and/or peripheral nervous system; others influence epithelial transport and regulate the secretion and receptors of several humoral agents. This review summarizes the physiology of the different dopamine receptors in the regulation of blood pressure, and the relationship between dopamine receptor subtypes and hypertension.

scholarly journals The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 139
Author(s):  
Waleed N. Qaddumi ◽  
Pedro A. Jose
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Dopaminergic System ◽  
Receptor Subtypes ◽  
The Many ◽  
Renal Dopamine ◽  
Regulation Of Blood Pressure ◽  
And Oxidative Stress

The kidney is critical in the long-term regulation of blood pressure. Oxidative stress is one of the many factors that is accountable for the development of hypertension. The five dopamine receptor subtypes (D1R–D5R) have important roles in the regulation of blood pressure through several mechanisms, such as inhibition of oxidative stress. Dopamine receptors, including those expressed in the kidney, reduce oxidative stress by inhibiting the expression or action of receptors that increase oxidative stress. In addition, dopamine receptors stimulate the expression or action of receptors that decrease oxidative stress. This article examines the importance and relationship between the renal dopaminergic system and oxidative stress in the regulation of renal sodium handling and blood pressure. It discusses the current information on renal dopamine receptor-mediated antioxidative network, which includes the production of reactive oxygen species and abnormalities of renal dopamine receptors. Recognizing the mechanisms by which renal dopamine receptors regulate oxidative stress and their degree of influence on the pathogenesis of hypertension would further advance the understanding of the pathophysiology of hypertension.

scholarly journals Molecular modelling of D2-like dopamine receptors

1992 ◽  
Vol 287 (1) ◽  
pp. 277-282 ◽  
Author(s):  
C D Livingstone ◽  
P G Strange ◽  
L H Naylor
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Three Dimensional ◽  
Transmembrane Domains ◽  
Receptor Subtypes ◽  
Alpha Helices ◽  
Dopamine Receptor Subtypes ◽  
Membrane Bound ◽  
Agonist Ligands ◽  
Sequence Similarities

Three-dimensional computer models of the rat D2, D3 and D4 dopamine receptor subtypes have been constructed based on the diffraction co-ordinates for bacteriorhodopsin, another membrane-bound protein containing seven transmembrane domains presumed to be arranged in a similar spatial orientation. Models were assembled by aligning the putative transmembrane domains of the dopamine receptors with those of bacteriorhodopsin using sequence similarities, and then superimposing these modelled alpha-helices on to the bacteriorhodopsin-derived co-ordinates. These models explore the potential hydrogen bonding, electrostatic and stacking interactions within the receptor which may be important for maintaining the conformation of these receptors, and thereby provide target sites for agonist binding. Proposed interactions between the catecholamine ligands and these receptors appear to account for the affinity, although not the specificity, of these agonist ligands for the different dopamine receptor subtypes. Such models will be useful for establishing structure-function relationships between ligands and the dopamine receptors, and may ultimately provide a template for the design of receptor-specific drugs.

scholarly journals Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice

2008 ◽  
Vol 294 (2) ◽  
pp. H551-H569 ◽  
Author(s):  
Chunyu Zeng ◽  
Ines Armando ◽  
Yingjin Luo ◽  
Gilbert M. Eisner ◽  
Robin A. Felder ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Physiological Role ◽  
G Protein Coupled Receptors ◽  
Receptor Subtypes ◽  
Humoral Factors ◽  
Dopamine Receptor Subtypes ◽  
Receptor Mutant ◽  
G Protein Coupled ◽  
Regulation Of Blood Pressure

Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral factors, such as aldosterone, angiotensin, catecholamines, endothelin, oxytocin, prolactin pro-opiomelancortin, reactive oxygen species, renin, and vasopressin. Dopamine receptors are classified into D1-like (D1 and D5) and D2-like (D2, D3, and D4) subtypes based on their structure and pharmacology. In recent years, mice deficient in one or more of the five dopamine receptor subtypes have been generated, leading to a better understanding of the physiological role of each of the dopamine receptor subtypes. This review summarizes the results from studies of various dopamine receptor mutant mice on the role of individual dopamine receptor subtypes and their interactions with other G protein-coupled receptors in the regulation of blood pressure.

scholarly journals Differential receptor crosstalk in DRD1-DRD2 heterodimer upon phasic and tonic dopamine signals

2021 ◽  
Author(s):  
Hyunbin Kim ◽  
Min-Ho Nam ◽  
Sohyeon Jeong ◽  
Hyowon Lee ◽  
Soo-Jin Oh ◽  
...  
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Camp Level ◽  
Receptor Subtypes ◽  
Dopamine Level ◽  
Individual Activity ◽  
Time Activity ◽  
Downstream Signaling ◽  
Receptor Crosstalk

In response to phasic and tonic release, dopamine neurotransmission is regulated by its receptor subtypes, mainly dopamine receptor type 1 and 2 (DRD1 and DRD2). These dopamine receptors are known to form a heterodimer, however the receptor crosstalk between DRD1 and DRD2 was only suspected by measuring their downstream signaling products, due to the lack of methodology for selectively detecting individual activity of different dopamine receptors. Here, we develop red DRD1 sensor (R-DRD1) and green DRD2 sensor (G-DRD2) which can specifically monitor the real-time activity of DRD1 and DRD2, and apply these multicolor sensors to directly measure the receptor crosstalk in the DRD1-DRD2 heterodimer. Surprisingly, we discover that DRD1 activation in the heterodimer is inhibited only at micromolar phasic concentration of dopamine, while DRD2 activation is selectively inhibited at nanomolar tonic dopamine level. Differential receptor crosstalk in the DRD1-DRD2 heterodimer further modulates their downstream cAMP level. These data imply a novel function of the DRD1-DRD2 heterodimer at physiological dopamine levels of phasic and tonic release. Our approach utilizing multicolor receptor sensors will be useful to discover novel function of GPCR heterodimers.

Abstract 370: Upregulation of Renal D5 Dopamine Receptor Ameliorates Hypertension in D3 Deficient Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Xiaoyan Wang ◽  
Crisanto S Escano ◽  
Laureano Asico ◽  
John E Jones ◽  
Alan Barte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Deficient Mice

D 3 dopamine receptor (D 3 R) deficient mice have renin-dependent hypertension but the hypertension is mild and is not associated with oxidative stress. In order to determine if any compensatory mechanism in the kidney is involved in the regulation of blood pressure with disruption of D 3 R, we measured the renal protein expression of dopamine receptors in D 3 R homozygous (D 3 -/-) and heterozygous (D 3 +/-) knockout mice and their wild type (D 3 +/+) littermates. D 5 dopamine receptor (D 5 R) (169±23%, reported as % of D 3 +/+, n=5/group) expression was increased but D 4 dopamine receptors protein expression (59±8%) was decreased, while no significant changes were found with D 1 and D 2 dopamine receptors. Immunocytochemistry showed a stronger renal staining of D 5 R but without a change in renal tubule cell distribution in D 3 -/- relative to D 3 +/+ mice. D 5 R abundance was also increased in D 3 +/- (205±30%, n=5/group) relative to D 3 +/+ mice, while D 1 R abundance was similar between D 3 +/- and D 3 +/+ mice. The increase in D 5 R expression was abolished while blood pressure was increased further in D 3 -/- mice fed a high salt diet. Treatment of the D 1 -like (including D 1 and D 5 receptors) antagonist, SCH23390 , increased the blood pressure to a greater extent in anesthetized D 3 -/- mice than in D 3 +/+ mice (n=4/group), suggesting that the upregulation of D 5 R may modulate the hypertension in mice caused by the disruption of D 3 R. Since dopamine inhibits the NADPH oxidase-induced production of reactive oxygen species (ROS) via the D 5 R, we also measured the protein expression of NOXs in the kidney and isoprostane in the urine. No NADPH oxidase subunit was increased in D 3 -/- and D 3 +/- mice relative to D 3 +/+ mice fed a normal or salt high salt diet, and urinary isoprostane excretion was also similar in D 3 -/- and D 3 +/+ mice. Our findings suggest that the upregulation of D 5 R may minimize the hypertension and prevent oxidative stress in D 3 -/- mice.

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