ATP-diphosphohydrolase activity in rat renal microvillar membranes and vascular tissue

Sandoval, Sebastián Salazar; Garcı́a, Lorena; Mancilla, Marta; Kettlun, Ana M.; Collados, L.; Chayet, L.; Álvarez, Álvaro; Traverso-Cori, A.; Valenzuela, Manuel

doi:10.1016/1357-2725(95)00153-0

Cited by 15 publications

(10 citation statements)

References 33 publications

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“…ATP (and ADP)-degrading enzymes which comprise the families of ectonucleotide triphosphate diphosphohydrolases (NTPDase, NTPDase1-8) and ectonucleotide pyrophosphatase phosphodiesterases (NPPs, NPP1-3) are widely expressed in many tissues including the kidney (Chadwick & Frischauf 1997, Kegel et al 1997, Vekaria et al 2006). NTP-Dase1 was shown to be localized in the brush border of the proximal tubule, throughout the renal vasculature and in mesangial cells (Sandoval et al 1996, Kishore et al 2005, Vekaria et al 2006. Immunohistochemistry also revealed high expression of ectonucleotide pyrophosphatase phosphodiesterases (NPP3) in the glomerulus (Vekaria et al 2006).…”

Section: Atp Degrading Enzymes In the Jgamentioning

confidence: 97%

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Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine

Castrop

2006

Acta Physiologica

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In the juxtaglomerular apparatus of the kidney the loop of Henle gets into close contact to its parent glomerulus. This anatomical link between the tubular system and the vasculature of the afferent and efferent arteriole enables specialized tubular cells, the macula densa (MD) cells, to establish an intra-nephron feedback loop designed to control preglomerular resistance and thereby single nephron glomerular filtration rate. This review focuses on the signalling mechanisms which link salt-sensing MD cells and the regulation of preglomerular resistance, a feedback loop known as tubuloglomerular feedback (TGF). Two purinergic molecules, ATP and adenosine, have emerged over the years as most likely candidates to serve as mediators of TGF. Data will be reviewed supporting a role of either ATP or adenosine as mediators of TGF. In addition, a concept will be discussed that integrates both ATP and adenosine into one signalling cascade that includes (i) release of ATP from MD cells upon increases in tubular salt concentration, (ii) extracellular degradation of ATP to form adenosine, and (iii) adenosinemediated vasoconstriction of the afferent arteriole.

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Section: Atp Degrading Enzymes In the Jgamentioning

confidence: 97%

“…2006). NTPDase1 was shown to be localized in the brush border of the proximal tubule, throughout the renal vasculature and in mesangial cells (Sandoval et al. 1996, Kishore et al.…”

Section: Tubuloglomerular Feedback: Cooperation Of Atp and Adenosinementioning

confidence: 99%

Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine

Castrop

2006

Acta Physiologica

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“…It is likely that ecto-ATPases dephosphorylating ATP to AMP are present in cells adjacent to the MD. ATP-diphosphohydrolase activity is associated with most endothelial cells, including those in the renal vasculature (19,24). Furthermore, NTPDase2 (CD39L1), one of the nucleoside triphosphate diphosphohydrolases converting ATP and ADP to AMP, has been found in association with MD cells and renal arterioles (S.C. Robson, personal communication).…”

Section: Figurementioning

confidence: 99%

Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73–deficient mice

Castrop¹,

Huang²,

Hashimoto³

et al. 2004

J. Clin. Invest.

166

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Adenosine coordinates organ metabolism and blood supply, and it modulates immune responses. In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR. To determine whether adenosine formation depends on extracellular nucleotide hydrolysis, we studied NaCl-dependent GFR regulation (tubuloglomerular feedback) in mice with targeted deletion of ecto-5′-nucleotidase/CD73 (e-5′NT/CD73), the enzyme responsible for adenosine formation from AMP. e-5′NT/CD73 -/-mice were viable and showed no gross anatomical abnormalities. Blood pressure, blood and urine chemistry, and renal blood flow were not different between e-5′NT/CD73 +/+ and e-5′NT/CD73 -/-mice. e-5′NT/CD73 -/-mice had a significantly reduced fall in stop flow pressure and superficial nephron glomerular filtration rate in response to a saturating increase of tubular perfusion flow. Furthermore, whereas tubuloglomerular feedback responses did not change significantly during prolonged loop of Henle perfusion in e-5′NT/CD73 +/+ mice, a complete disappearance of the residual feedback response was noted in e-5′NT/CD73 -/-mice over 10 minutes of perfusion. The contractile response of isolated afferent arterioles to adenosine was normal in e-5′NT/CD73 -/-mice. We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5′NT/CD73-mediated dephosphorylation of 5′-AMP, presumably generated from released ATP. IntroductionAdenosine is a multifunctional nucleoside that coordinates cellular oxygen supply and demand by adapting organ blood flow to metabolic rate (1). In addition, adenosine plays a major role in immune responsiveness with its net effect being either pro-or anti-inflammatory, depending on adenosine receptor subtype representation (2). Studies in adenosine receptor KO mice have contributed importantly to further defining nonredundant roles of adenosine in both processes. Our focus has been to elucidate the role of adenosine in the local hemodynamic control mechanism, called tubuloglomerular feedback, that operates in the kidney at the level of the juxtaglomerular apparatus (JGA). Tubuloglomerular feedback describes a functional connection between the tubular epithelium at the site of the macula densa (MD) and the underlying smooth muscle cells of the afferent and efferent glomerular arterioles. An increase in NaCl concentration in the luminal fluid at the MD cells causes an activation of smooth muscle cells and arteriolar vasoconstriction. As a consequence, glomerular filtration pressure and filtration rate fall. Both pharmacological and gene-targeting approaches have shown that tubuloglomerular feedback-induced vasoconstriction has an absolute requirement for functional A1 adenosine receptors (A1ARs), suggesting that adenosine as their natural ligand

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“…More likely, however, nucleotides are secreted under basal conditions and in response to a variety of mechanical, osmotic, and chemical stimuli by most-if not all-cells of the glomerulus and its associated vasculature, as well as the proximal tubule cells rich in mitochondria [4][5][6]. Ecto-ATPases and ectoadenosine 5′ diphosphatases (ADPases) are also present throughout the nephron [7][8][9][10][11][12], although their nephron-specific localization has not been studied in depth. Their action generates metabolites that are also active at P2 receptors [ADP and uridine 5′ diphosphate (UDP)] [13][14][15].…”

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confidence: 99%

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Hovater

Olteanu

Welty

et al. 2008

Purinergic Signalling

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The nephron is the functional unit of the kidney. Blood and plasma are continually filtered within the glomeruli that begin each nephron. Adenosine 5′ triphosphate (ATP) and its metabolites are freely filtered by each glomerulus and enter the lumen of each nephron beginning at the proximal convoluted tubule (PCT). Flow rate, osmolality, and other mechanical or chemical stimuli for ATP secretion are present in each nephron segment. These ATP-release stimuli are also different in each nephron segment due to water or salt permeability or impermeability along different luminal membranes of the cells that line each nephron segment. Each of the above stimuli can trigger additional ATP release into the lumen of a nephron segment. Each nephron-lining epithelial cell is a potential source of secreted ATP. Together with filtered ATP and its metabolites derived from the glomerulus, secreted ATP and adenosine derived from cells along the nephron are likely the principal two of several nucleotide and nucleoside candidates for renal autocrine and paracrine ligands within the tubular fluid of the nephron. This minireview discusses the first principles of purinergic signaling as they relate to the nephron and the urinary bladder. The review discusses how the lumen of a renal tubule presents an ideal purinergic signaling microenvironment. The review also illustrates how remodeled and encapsulated cysts in autosomal dominant polycystic kidney disease (ADPKD) and remodeled pseudocysts in autosomal recessive PKD (ARPKD) of the renal collecting duct likely create an even more ideal microenvironment for purinergic signaling. Once trapped in these closed microenvironments, purinergic signaling becomes chronic and likely plays a significant epigenetic and detrimental role in the secondary progression of PKD, once the remodeling of the renal tissue has begun. In PKD cystic microenvironments, we argue that normal purinergic signaling within the lumen of the nephron provides detrimental acceleration of ADPKD once remodeling is complete.

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ATP-diphosphohydrolase activity in rat renal microvillar membranes and vascular tissue

Cited by 15 publications

References 33 publications

Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine

Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine

Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73–deficient mice

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

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