Both Extracellular Atp and Shear Stress Regulate the Release of Nitric Oxide in Rat Caudal Artery

Kwon, Young Mi; Shinozuka, Kazumasa; Kagota, Satomi; Yamaguchi, Yu; Nakamura, Kazuki; Kunitomo, Masaru

doi:10.1046/j.1440-1681.1999.03062.x

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…Our goal was to clarify a signaling pathway that remains unknown in many types of cells, including those of the thick ascending limb. In vascular endothelial cells, ATP released by physical and chemical stimuli increases endothelium-derived NO (22). Similarly, ATP released from red blood cells in the lung vasculature stimulates NO production by endothelial cells (37).…”

Section: Discussionmentioning

confidence: 99%

Akt1 mediates purinergic-dependent NOS3 activation in thick ascending limbs

Silva

Garvin

2009

American Journal of Physiology-Renal Physiology

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Silva GB, Garvin JL. Akt1 mediates purinergic-dependent NOS3 activation in thick ascending limbs. Am J Physiol Renal Physiol 297: F646 -F652, 2009. First published July 1, 2009 doi:10.1152/ajprenal.00270.2009.-Extracellular ATP regulates many physiological processes via release of nitric oxide (NO). ATP stimulates NO in thick ascending limbs (TALs), but the signaling cascade involved in the cells of this nephron segment, as well as many other types of cells, is poorly understood. We hypothesized that ATP enhances NO synthase (NOS) activity by stimulating PI3 kinase and Akt. We measured 1) NO in TALs using the NO-sensitive dye DAF-2 DA and 2) Akt activity by fluorescence resonance energy transfer and phosphorylation of Akt isoforms. ATP (100 M) stimulated NO in wild-type mice [26 Ϯ 4 arbitrary units (AU)], but not in NOS3 Ϫ/Ϫ mice (2 Ϯ 2 AU; P Ͻ 0.04). In the presence of the NOS1-and NOS2-selective inhibitors 7-NI and 1400W, ATP stimulated NO by 30 Ϯ 2 and 33 Ϯ 3 AU, respectively (not significant vs. control). In the presence of the PI3 kinase inhibitor LY294002, ATP-increased NO was reduced by 85% (5 Ϯ 2 vs. 28 Ϯ 4 AU; P Ͻ 0.02). ATP alone increased Akt activity and this effect was significantly blocked by suramin, a P2 receptor antagonist. In the presence of an Akt-selective inhibitor, ATP-induced NO was blocked by 90 Ϯ 4%. ATP significantly stimulated Akt1 phosphorylation at Ser 473 by 91 Ϯ 13%, whereas Akt2 phosphorylation remained unchanged and Akt3 phosphorylation decreased. In vivo transduction of TALs with a dominantnegative Akt1 significantly decreased ATP-induced NO by 88 Ϯ 6%. We concluded that ATP increases NOS3-derived NO via Akt1 activation in the TAL. purinergic signaling; adenosine triphosphate; Na-K-2Cl cotransporter IN THE KIDNEY, ADENOSINE triphosphate (ATP) is released from several types of cells. Macula densa cells release ATP in response to an increase in luminal NaCl (19), while mesangial cells release ATP in response to elevated glucose (35). The cells that constitute the thick ascending limb release ATP in response to decreases in osmolality (34) and increases in luminal flow (16). The ATP released from these and other cells has pleotrophic effects. In vivo studies showed that extracellular ATP inhibits fluid absorption (1). In the collecting duct extracellular ATP also decreases Na (32) and water (18) reabsorption. Increases in ATP in the renal interstitium correlate with decreases in renal blood flow (26), most likely related to afferent arterial autoregulation (14). Moreover, we recently demonstrated that extracellular ATP stimulates nitric oxide (NO) by thick ascending limbs via activation of purinergic 2X (P2X) receptors (33). Indeed, ATP has been shown to stimulate NO production in a variety of cells, including platelets (20), endothelial cells (37), and cells of the central nervous system (31). However, the mechanisms by which ATP stimulates NO production are poorly understood.Activation of P2X receptors may lead to stimulation of several signaling cascades. These include glycoge...

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Section: Discussionmentioning

confidence: 99%

Akt1 mediates purinergic-dependent NOS3 activation in thick ascending limbs

Silva

Garvin

2009

American Journal of Physiology-Renal Physiology

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“…Extracellular purinergic signaling by ATP and adenosine has been hypothesized to play a central role in modulation of skeletal muscle and renal blood flow and glomerular filtration rate in the kidney (19). Recent evidence also has suggested that "cross talk" may exist between purinergic signaling and nitric oxide signaling in vascular beds (22,24,29). These issues require further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…ATP release is potentiated by the Ca 2ϩ agonists ionomycin and thapsigargin. Because agonists that increase cytosolic Ca 2ϩ have profound effects on endothe-lial cell function, signaling, and production and on release of vasoactive mediators such as nitric oxide (22,24), we examined the effect of Ca 2ϩ agonists on ATP release across the apical membrane of HUVEC monolayers. Ionomycin (2 M), a Ca 2ϩ ionophore that promotes Ca 2ϩ influx into the cell from extracellular stores, elicited an immediate increase in ATP release (Fig.…”

Section: Endothelial Cells In Primary Culture Form Resistive Monolayementioning

confidence: 99%

Extracellular ATP signaling and P2X nucleotide receptors in monolayers of primary human vascular endothelial cells

Schwiebert

Rice

Kudlow

et al. 2002

American Journal of Physiology-Cell Physiology

127

106

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ATP and its metabolites regulate vascular tone; however, the sources of the ATP released in vascular beds are ill defined. As such, we tested the hypothesis that all limbs of an extracellular purinergic signaling system are present in vascular endothelial cells: ATP release, ATP receptors, and ATP receptor-triggered signal transduction. Primary cultures of human endothelial cells derived from multiple blood vessels were grown as monolayers and studied using a bioluminescence detection assay for ATP released into the medium. ATP is released constitutively and exclusively across the apical membrane under basal conditions. Hypotonic challenge or the calcium agonists ionomycin and thapsigargin stimulate ATP release in a reversible and regulated manner. To assess expression of P2X purinergic receptor channel subtypes (P2XRs), we performed degenerate RT-PCR, sequencing of the degenerate P2XR product, and immunoblotting with P2XR subtype-specific antibodies. Results revealed that P2X(4) and P2X(5) are expressed abundantly by endothelial cell primary cultures derived from multiple blood vessels. Together, these results suggest that components of an autocrine purinergic signaling loop exist in the endothelial cell microvasculature that may allow for "self-regulation" of endothelial cell function and modulation of vascular tone.

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“…ATP and shear stress (known to release ATP from endothelial cells, see Burnstock, 1999) release NO from rat tail artery endothelial cells, resulting in vasodilatation (Kwon et al, 1999). Hypotonic stress increased the [Ca 2+ ] i and outflow of ATP from endothelial cells of the rat tail artery, as well as increasing cell volume (Shinozuka et al, 2001).…”

Section: B Rat Tail Arterymentioning

confidence: 99%