Dopamine depolarizes podocytes via a D1-like receptor

Bek, Martin; Fischer, Karl-Georg; Greiber, S.; Hupfer, Charlotte; Mündel, Peter; Pavenstädt, Hermann

doi:10.1093/ndt/14.3.581

Cited by 23 publications

(17 citation statements)

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“…It is well known that vasoactive hormones, such as angiotensin II regulate cell function via ligand-receptor binding [25]. Podocytes express a variety of G-protein-coupled receptors, including metabotropic glutamate receptor 1, adrenergic β2 and Dopamine D1, which mediate an increase in cAMP upon stimulation [12], [26], [27]. Several lines of evidence indicate that the cAMP pathway affects podocyte biology.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that activation of the PKA pathway protects podocytes from injury. All-trans retinoic acid restores differentiation markers in HIV-infected podocytes via activation of the cAMP/PKA signaling pathway and the expression of nephrin in podocytes is regulated by cAMP/PKA [27], [33]. Oba S et al found that activation of PKA prevents PAN-induced ROS generation in podocytes [34].…”

Section: Discussionmentioning

confidence: 99%

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cAMP Signaling Prevents Podocyte Apoptosis via Activation of Protein Kinase A and Mitochondrial Fusion

Tao

Xie

et al. 2014

PLoS ONE

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Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

cAMP Signaling Prevents Podocyte Apoptosis via Activation of Protein Kinase A and Mitochondrial Fusion

Tao

Xie

et al. 2014

PLoS ONE

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“…It is well-recognized that the catecholamine dopamine plays important roles in blood pressure regulation by modulating renal blood flow, glomerular filtration rate, and epithelial sodium transport (22,29). Dopamine is synthesized in the proximal tubule and is released as a paracrine and autocrine hormone to act on different receptors in the renal tubules, glomeruli, and renal blood vessels (2,29). Dopamine exerts profound effects on renal hemodynamics in a dosedependant manner (22,29).…”

Section: Discussionmentioning

confidence: 99%

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Li¹,

Zhou²,

Kalhorn³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…They are not found in the glomerulus [19], although they are expressed in mouse glomerular podocytes in culture [34]. D1R, but not D5R, is expressed in the macula densa and juxtaglomerular cells in rats [35].…”

Section: Renal Dopamine Receptor Regulation Of Oxidative Stressmentioning

confidence: 99%

Renal Dopamine Receptors, Oxidative Stress, and Hypertension

Cuevas

Villar

José

et al. 2013

IJMS

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Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1), paraoxonase 2 (PON2), and heme oxygenase 2 (HO-2), all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice.

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Dopamine depolarizes podocytes via a D1-like receptor

Abstract: The data indicate that dopamine induces a cAMP-dependent depolarization via a D1-like receptor in podocytes.

Cited by 23 publications

References 1 publication

cAMP Signaling Prevents Podocyte Apoptosis via Activation of Protein Kinase A and Mitochondrial Fusion

cAMP Signaling Prevents Podocyte Apoptosis via Activation of Protein Kinase A and Mitochondrial Fusion

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Renal Dopamine Receptors, Oxidative Stress, and Hypertension

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