Potential Functional Roles of Extracellular ATP in Kidney and Urinary Tract

Chan, Choong Meng; Unwin, Robert J.; Burnstock, Geoffrey

doi:10.1159/000020524

Cited by 59 publications

(63 citation statements)

References 44 publications

(61 reference statements)

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“…In the glomerular vasculature, the existence of P2-purinoceptors, mainly P2Y, has been confirmed in cultured endothelial cells and smooth muscle-like glomerular mesangial cells. 18 It is commonly documented that activation of P2Y-purinoceptors by ATP leads to an intracellular increase in [Ca 2ϩ ] through the phospholipase-C/inositol-1,4,5-triphospahte (IP 3 ) pathway. 9,18 The eNOS activity can be increased by a Ca 2ϩ /calmodulin-dependent or kinasedependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…18 It is commonly documented that activation of P2Y-purinoceptors by ATP leads to an intracellular increase in [Ca 2ϩ ] through the phospholipase-C/inositol-1,4,5-triphospahte (IP 3 ) pathway. 9,18 The eNOS activity can be increased by a Ca 2ϩ /calmodulin-dependent or kinasedependent mechanism. It has been previously demonstrated that nebivolol itself or its putative endogenous mediator could induce an IP 3 /Ca 2ϩ -dependent activation of eNOS in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Third-Generation β-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux

et al. 2003

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Background-Nebivolol and carvedilol are third-generation ␤-adrenoreceptor antagonists, which unlike classic ␤-blockers, have additional endothelium-dependent vasodilating properties specifically related to microcirculation by a molecular mechanism that still remains unclear. We hypothesized that nebivolol and carvedilol stimulate NO release from microvascular endothelial cells by extracellular ATP, which is a well-established potent autocrine and paracrine signaling factor modulating a variety of cellular functions through the activation of P2-purinoceptors. Methods and Results-Contraction and relaxation of renal glomerular vasculature were measured by determination of intracapillary volume with [ 3 H]-inulin. Biologically active NO was measured with highly sensitive porphyrinic NO microsensors in a single glomerular endothelial cell (GEC). Extracellular ATP was measured by a luciferin-luciferase assay. Enzymatic degradation of extracellular ATP by apyrase and blockade of P2Y-purinoceptors by suramin or reactive blue 2 inhibited both ␤-blocker-induced glomerular vasorelaxations and ␤-blocker-stimulated NO release from GECs. Both ␤-blocker-induced vasorelaxations were in the micromolar concentration range identical to that required for the ␤-blocker stimulation of ATP and NO release from GECs. The maximum of NO release for nebivolol and carvedilol was very similar (188Ϯ14 and 226Ϯ17, respectively). Blockade of ATP release by a mechanosensitive ion channel blocker, Gd 3ϩ , inhibited the ␤-blocker-dependent release of ATP and NO from GECs. Conclusions-These results demonstrate for the first time that nebivolol and carvedilol induce relaxation of renal glomerular microvasculature through ATP efflux with consequent stimulation of P2Y-purinoceptor-mediated NO

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Third-Generation β-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux

et al. 2003

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“…Pharmacological studies with various ATP analogues have demonstrated two major groups of purinergic (P2) receptors: ionotropic receptors (P2X), associated with ligand-gated nonselective cation channel activity, and metabotropic receptors (P2Y), associated with activation of Gproteins (2)(3)(4)(5). In nonexcitable cells, extracellular ATP induces an elevation of cytosolic [Ca 2ϩ ] ([Ca 2ϩ ] i ) by two distinct mechanisms, either by activation of Ca 2ϩ release from intracellular Ca 2ϩ stores or via activation of Ca 2ϩ influx from the external medium (5,6). The P2Y subtype is coupled via G ␣q/11 to the activation of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C. Thus, activation of these receptors by ATP leads to an increase in [Ca 2ϩ ] i due to increase in inositol 1,4,5-trisphosphate (IP 3 ) 1 and IP 3 -mediated internal Ca 2ϩ release.…”

Section: (I) Romk1 and The Cystic Fibrosis Transmembrane Regulator Prmentioning

confidence: 99%

ATP-dependent Activation of KCa and ROMK-type KATP Channels in Human Submandibular Gland Ductal Cells

Liu

Singh

Ambudkar³

1999

Journal of Biological Chemistry

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“…When extracellular ATP and other nucleotides reach even low micromolar concentrations locally, they stimulate a variety of P2 receptors, eliciting short-and long-term biological effects. In recent years, the potential roles of extracellular nucleotides in the regulation of renal tubular transport, especially salt and water, through P2 receptors are increasingly being recognised [15][16][17][18][19][20][21].…”

Section: Physiology Of the P2y 2 Receptor In The Collecting Ductmentioning

confidence: 99%

P2Y2 receptors and water transport in the kidney

Kishore

Nelson

Miller

et al. 2009

Purinergic Signalling

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The kidneys play a critical role in the maintenance of water homeostasis. This is achieved by the inherent architecture of the nephron along with the expression of various membrane transporters and channels that are responsible for the vectorial transport of salt and water. The collecting duct has become a focus of attention by virtue of its ability to transport water independent of solutes (free-water transport), and its apparent involvement in various water balance disorders. It was originally believed that the water transport capability of the collecting duct was solely under the influence of the circulating hormone, arginine vasopressin (AVP). However, during the past decade, locally produced autocrine and/or paracrine factors have emerged as potent modulators of transport of water by the collecting duct. Recently, much attention has been focused on the purinergic regulation of renal water transport. This review focuses on the role of the P2Y 2 receptor, the predominant purinergic receptor expressed in the collecting duct, in the modulation of water transport in physiological and pathophysiological conditions, and its therapeutic potential as a drug target to treat water balance disorders in the clinic. Studies carried out by us and other investigators are unravelling potent interactions among AVP, prostanoid and purinergic systems in the medullary collecting duct, and the perturbations of these interactions in water balance disorders such as acquired nephrogenic diabetes insipidus. Future studies should address the potential therapeutic benefits of modulators of P2Y 2 receptor signalling in water balance disorders, which are extremely prevalent in hospitalised patients irrespective of the underlying pathology.

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Potential Functional Roles of Extracellular ATP in Kidney and Urinary Tract

Cited by 59 publications

References 44 publications

Third-Generation β-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux

Third-Generation β-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux

ATP-dependent Activation of KCa and ROMK-type KATP Channels in Human Submandibular Gland Ductal Cells

P2Y2 receptors and water transport in the kidney

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