Stimulation of the proximal tubule Na+-ATPase activity by adenosine A2A receptor

Wengert, Mira; Bertó, Carolina Gessinger; Kaufman, J.; Leão-Ferreira, L.R.; Paes‐de‐Carvalho, Roberto; Lopes, Anibal Gil; Caruso-Neves, Celso

doi:10.1016/j.biocel.2004.06.006

Cited by 25 publications

(16 citation statements)

References 29 publications

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“…In the kidney, extracellular adenosine is an autocrine/paracrine modulator of several physiological functions including sodium excretion [38]. It has been proposed that the adenosine A 1 and A 2A receptors regulate at least in part active sodium transport along the nephron by Na + /K + ATPase [39, 40]. We propose that these mechanisms seen in other tissues may also be present in the placenta.…”

Section: Discussionmentioning

confidence: 93%

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Versen‐Höynck¹,

Rajakumar²,

Bainbridge³

et al. 2009

Placenta

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Placental hypoxia as a result of impaired trophoblast invasion is suggested to be involved in the pathophysiology of preeclampsia. Hypoxia is a potent stimulus for the release of adenosine, and the actions of adenosine are mediated through four adenosine receptors, A 1 , A 2A , A 2B and A 3 . We investigated the presence, distribution and expression of adenosine receptor subtypes in the human placenta, the expression of the adenosine receptors in placentas from pregnancies complicated by preeclampsia, small for gestational age (SGA) infants and uncomplicated pregnancies, and the effect of hypoxia on placental adenosine receptor expression. Immunofluorescent microscopy localized A 1 , A 2A , A 2B and A 3 adenosine receptors to the syncytiotrophoblast, endothelial cells and myo-/ fibroblasts within the human placenta. Adenosine receptor protein and message expression levels were significantly higher in placentas from preeclamptic pregnancies with or without SGA infants, but not different in pregnancies with SGA infants alone. In vitro exposure of placental villous explants to hypoxia (2% oxygen) increased the expression of A 2A adenosine receptor 50%. These data indicate that all four known adenosine receptors are expressed in the human placenta and adenosine receptor expression is significantly higher in pregnancies complicated by preeclampsia. These data are consistent with the hypothesis that differences in placental adenosine receptors may contribute to alterations in placental function in preeclampsia.

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Section: Discussionmentioning

confidence: 93%

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Versen‐Höynck¹,

Rajakumar²,

Bainbridge³

et al. 2009

Placenta

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“…A 1 receptors were characterised in human proximal tubule epithelial (HK-2) cells [367]. In the pig proximal tubule, Na + -ATPase activity is stimulated via adenosine A 2A receptors, thus regulating sodium reabsorption [406]. Transepithelial fluxes of adenosine across human proximal tubule cells involve specific nucleoside transporters [80].…”

Section: Renal Tubulesmentioning

confidence: 99%

Purinergic signalling in the kidney in health and disease

Burnstock

Evans

Bailey

2013

Purinergic Signalling

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The involvement of purinergic signalling in kidney physiology and pathophysiology is rapidly gaining recognition and this is a comprehensive review of early and recent publications in the field. Purinergic signalling involvement is described in several important intrarenal regulatory mechanisms, including tuboglomerular feedback, the autoregulatory response of the glomerular and extraglomerular microcirculation and the control of renin release. Furthermore, purinergic signalling influences water and electrolyte transport in all segments of the renal tubule. Reports about purine-and pyrimidine-mediated actions in diseases of the kidney, including polycystic kidney disease, nephritis, diabetes, hypertension and nephrotoxicant injury are covered and possible purinergic therapeutic strategies discussed.

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“…In the proximal tubule, adenosine decreases the activity of the ouabain-insensitive Na + -ATPase interacting with A1 subtype receptors through G i protein pathway, without effect on the Na + /K + -ATPase [22]. Furthermore, in the presence of A1 selective antagonist, adenosine stimulates the Na + -ATPase, effect mediated by A2A receptors through PKA pathway [179]. …”

Section: Modulation Of the Na+-atpase Activitymentioning

confidence: 99%

“…Although the activation of PKA- or PKC-signaling pathways separately stimulates the Na + -ATPase activity [131, 179], the PKA pathway seems to be involved in a negative modulation of PKC-stimulatory effect when both ways are sequentially activated [63, 64]. Thus, the stimulatory effect of Ang II, mediated by PKC pathway, is reversed by adenosine through PKA pathway [63, 64].…”

Section: Modulation Of the Na+-atpase Activitymentioning

confidence: 99%

The second sodium pump: from the function to the gene

Rocafull

Thomas

Castillo

2012

Pflugers Arch - Eur J Physiol

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Transepithelial Na+ transport is mediated by passive Na+ entry across the luminal membrane and exit through the basolateral membrane by two active mechanisms: the Na+/K+ pump and the second sodium pump. These processes are associated with the ouabain-sensitive Na+/K+-ATPase and the ouabain-insensitive, furosemide-inhibitable Na+-ATPase, respectively. Over the last 40 years, the second sodium pump has not been successfully associated with any particular membrane protein. Recently, however, purification and cloning of intestinal α-subunit of the Na+-ATPase from guinea pig allowed us to define it as a unique biochemical and molecular entity. The Na+- and Na+/K+-ATPase genes are at the same locus, atp1a1, but have independent promoters and some different exons. Herein, we spotlight the functional characteristics of the second sodium pump, and the associated Na+-ATPase, in the context of its role in transepithelial transport and its response to a variety of physiological and pathophysiological conditions. Identification of the Na+-ATPase gene (atna) allowed us, using a bioinformatics approach, to explore the tertiary structure of the protein in relation to other P-type ATPases and to predict regulatory sites in the promoter region. Potential regulatory sites linked to inflammation and cellular stress were identified in the atna gene. In addition, a human atna ortholog was recognized. Finally, experimental data obtained using spontaneously hypertensive rats suggest that the Na+-ATPase could play a role in the pathogenesis of essential hypertension. Thus, the participation of the second sodium pump in transepithelial Na+ transport and cellular Na+ homeostasis leads us to reconsider its role in health and disease.

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Stimulation of the proximal tubule Na+-ATPase activity by adenosine A2A receptor

Cited by 25 publications

References 29 publications

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Purinergic signalling in the kidney in health and disease

The second sodium pump: from the function to the gene

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