Dopamine D2 Receptor Modulates Sodium Handling via Local Production of Dopamine in the Kidney

Ozono, Ryoji; Ueda, Atsushi; Oishi, Yoshihiko; Yano, Ai; Kambe, Masayuki; Katsuki, Motoya; Oshima, Tetsuya

doi:10.1097/00005344-200312001-00017

Cited by 16 publications

(17 citation statements)

References 27 publications

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“…Administration of dopamine can restore urine volume and sodium excretion of D 2 −/− mice to a level similar to that observed in D 2 +/+ mice. These results indicate that D 2 receptors play a significant role in renal local dopamine synthesis and that a decreased renal production of dopamine is, at least in part, responsible for the suppression of urine volume and sodium excretion in D 2 −/− mice [164].…”

Section: Physiological Role Of D 2 Receptormentioning

confidence: 78%

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The dopaminergic system in hypertension

et al. 2007

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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 D(1)-like (D(1) and D(5)) and D(2)-like (D(2), D(3) and D(4)) 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.

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Section: Physiological Role Of D 2 Receptormentioning

confidence: 78%

“…As compared with wild-type mice, renal local dopamine synthesis is reduced in D 2 −/− mice [164]. The activity of AADC, which converts l-DOPA into dopamine, is suppressed in D 2 −/− mice, and is accompanied by lower basal urine flow and sodium excretion.…”

Section: Physiological Role Of D 2 Receptormentioning

confidence: 91%

The dopaminergic system in hypertension

et al. 2007

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“…Germline deletion of D 2 R can result in salt-sensitive hypertension, that may be mouse strain dependent (41). The role of sodium balance in the hypertension associated with DJ-1 deficiency remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Role of Nuclear Factor Erythroid 2–Related Factor 2 in the Oxidative Stress–Dependent Hypertension Associated With the Depletion of DJ-1

Cuevas

Konkalmatt

et al. 2015

Hypertension

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Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure. We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor Nrf2 regulates the expression of several antioxidant genes. We tested the hypothesis that Nrf2 is involved in the renal DJ-1-mediated inhibition of reactive oxygen species production. We have reported that silencing dopamine 2 receptor in mouse renal proximal tubule cells decreases the expression of DJ-1. We now report that silencing DJ-1 or dopamine 2 receptor in mouse proximal tubule cells and mouse kidneys, decreases Nrf2 expression and activity and increases reactive oxygen species production; blood pressure is also increased in mice in which renal DJ-1 or dopamine 2 receptor is silenced. DJ-1−/− mice have decreased renal Nrf2 expression and activity, and increased nitro-tyrosine levels an dopamine 2 receptor d blood pressure. Silencing Nrf2 in mouse proximal tubule cells does not alter the expression of DJ-1 or dopamine 2 receptor, indicating that Nrf2 is downstream of dopamine 2 receptor and DJ-1. A Nrf2 inducer, bardoxolone, normalizes the systolic blood pressure and renal malondialdehyde levels in DJ-1−/− mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in DJ-1−/− mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and blood pressure.

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“…Distinct neuronal D2R circuits have been linked to the control of motor function, hormone release (Missale et al, 1998), and aggressive behavior (Miczek et al, 2002). In addition, mammalian D2-like receptors in renal tubules and the gastrointestinal tract have been implicated in sodium transport (Hussain et al, 1997;Ozono et al, 2003), and intestinal motility (Li et al, 2006), respectively.…”

Section: Discussionmentioning

confidence: 99%

Locomotor activity is regulated by D2‐like receptors in Drosophila: An anatomic and functional analysis

Draper

Kurshan

McBride

et al. 2007

Developmental Neurobiology

112

101

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In mammals, dopamine 2-like receptors are expressed in distinct pathways within the central nervous system, as well as in peripheral tissues. Selected neuronal D2-like receptors play a critical role in modulating locomotor activity and, as such, represent an important therapeutic target (e.g. in Parkinson's disease). Previous studies have established that proteins required for dopamine (DA) neurotransmission are highly conserved between mammals and the fruit fly Drosophila melanogaster. These include a fly dopamine 2-like receptor (DD2R; Hearn et al. PNAS 2002 99(22):14554) that has structural and pharmacologic similarity to the human D2-like (D2R). In the current study, we define the spatial expression pattern of DD2R, and functionally characterize flies with reduced DD2 receptor levels. We show that DD2R is expressed in the larval and adult nervous systems, in cell groups that include the Ap-let cohort of peptidergic neurons, as well as in peripheral tissues including the gut and Malpighian tubules. To examine DD2R function in vivo, we generated RNA-interference (RNAi) flies with reduced DD2R expression. Behavioral analysis revealed that these flies show significantly decreased locomotor activity, similar to the phenotype observed in mammals with reduced D2R expression. The fly RNAi phenotype can be rescued by administration of the DD2R synthetic agonist bromocriptine, indicating specificity for the RNAi effect. These results suggest Drosophila as a useful system for future studies aimed at identifying modifiers of dopaminergic signaling/locomotor function.

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Dopamine D2 Receptor Modulates Sodium Handling via Local Production of Dopamine in the Kidney

Cited by 16 publications

References 27 publications

The dopaminergic system in hypertension

The dopaminergic system in hypertension

Role of Nuclear Factor Erythroid 2–Related Factor 2 in the Oxidative Stress–Dependent Hypertension Associated With the Depletion of DJ-1

Locomotor activity is regulated by D2‐like receptors in Drosophila: An anatomic and functional analysis

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