P2X<sub>4</sub> receptors mediate ATP-induced calcium influx  in human vascular endothelial cells

Yamamoto, Kimiko; Korenaga, Risa; Kamiya, Akira; Qi, Zhi; Sokabe, Masahiro; Ando, Jun

doi:10.1152/ajpheart.2000.279.1.h285

Cited by 177 publications

(133 citation statements)

References 22 publications

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“…This ATP-induced ATP release may also be mediated by pannexin 1 channels, because they can be activated by extracellular ATP when coexpressed with P2Y receptors (13). ATP in blood vessels also interacts with P2Y receptors on endothelial cells, initiating a propagated calcium wave that ultimately leads to the release of nitric oxide onto vascular smooth muscle (31,32). Relaxation of the muscle leads to increased perfusion.…”

Section: Discussionmentioning

confidence: 99%

Pannexin 1 in erythrocytes: Function without a gap

Locovei

Dahl

2006

Proc. Natl. Acad. Sci. U.S.A.

466

644

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ATP is a widely used extracellular signaling molecule. The mechanism of ATP release from cells is presently unresolved and may be either vesicular or channel-mediated. Erythrocytes release ATP in response to low oxygen or to shear stress. In the absence of vesicles, the release has to be through channels. Erythrocytes do not form gap junctions. Yet, here we show with immunohistochemical and electrophysiological data that erythrocytes express the gap junction protein pannexin 1. This protein, in addition to forming gap junction channels in paired oocytes, can also form a mechanosensitive and ATP-permeable channel in the nonjunctional plasma membrane. Consistent with a role of pannexin 1 as an ATP release channel, ATP release by erythrocytes was attenuated by the gap junction blocker carbenoxolone. Furthermore, under conditions of ATP release, erythrocytes took up fluorescent tracer molecules permeant to gap junction channels.ATP release ͉ gap junction ͉ hemichannel ͉ dye uptake P annexins represent a recently discovered second family of gap junction proteins in vertebrates (1). Pannexins have no sequence homology with the well known connexin family of vertebrate gap junction proteins. Instead, they are related to innexins, which were originally considered to be exclusively invertebrate gap junction proteins. The functional role of pannexins is unknown. The existence of connexin-specific diseases, despite an overlap of connexin and pannexin expression, suggests a functional role of pannexins that is distinct from that of connexins. Pannexin 1, in addition to forming gap junctions in paired oocytes, also forms nonjunctional membrane channels that provide a passageway from the cytoplasm to the extracellular space for molecules in the size range of second messengers (2, 3). It can be hypothesized that the physiological role of pannexin 1 is formation of a nonjunctional membrane channel.Although the role of ATP as an extracellular signaling molecule is well recognized (4), the release mechanism for ATP from cells to the extracellular space has remained enigmatic. Two general release modes have been proposed: (i) vesicular release akin to the exocytotic release of transmitters and (ii) channel-mediated release. Although vesicular ATP release is well documented (5, 6), it cannot account for all of the ATP release phenomena. In particular, ATP is released from erythrocytes, which, under physiological conditions, are vesicle-free (7). Various channels have been implicated in the process, including CFTR (cystic fibrosis transmembrane conductance regulator), connexin 43 (Cx43) hemichannels, a volumeregulated channel (VRAC), and the purinergic receptor P2X7 (5,6,(8)(9)(10)(11). However, the evidence for their involvement falls short because of questionable specificity of the pharmacological blockers used to determine channel identity.Mechanical stress is a prime stimulus for ATP release in many cell types, including erythrocytes (12). An efficient release mechanism thus may involve a channel that is both mechanosensitive and...

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Section: Discussionmentioning

confidence: 99%

Pannexin 1 in erythrocytes: Function without a gap

Locovei

Dahl

2006

Proc. Natl. Acad. Sci. U.S.A.

466

644

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“…It is predominantly expressed in ECs cultured from human umbilical vein, pulmonary artery, aorta, and skin microvessels [38].…”

Section: P2x4 Purinoceptorsmentioning

confidence: 99%

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

Ngai¹

2012

TOCVJ

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Shear stress, the frictional drag on the endothelium from blood flow, is a major determinant of vascular physiology and pathology. Due to the pulsatile nature of blood flow, blood vessels are subjected to significant variations in mechanical forces. Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in detecting and responding to the mechanical forces generated by shear stress. Multiple sensing mechanisms are used by endothelial cells to detect changes in mechanical forces, leading to the activation of signaling networks. This review attempts to bring together recent findings on the mechanosensors present in the endothelial cells, and the regulation of endothelium-derived vasoactive autacoid production by shear stress.

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“…The P2X 4 receptor is the highest expressed P2 receptor in endothelium [79,80]. By using antisense oligonucleotides, the P2X 4 receptor was shown to be important for shear stress-dependent Ca 2+ influx via an ATP-dependent mechanism [81].…”

Section: Direction and Mechanism Of The Endothelial Flow Responsementioning

confidence: 99%

The touching story of purinergic signaling in epithelial and endothelial cells

Öhman

Erlinge

2012

Purinergic Signalling

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Endothelial and epithelial cells have something in commonthey are both the barrier and bridge between different environments. Forming a one-cell layer lining of blood vessels, airways, and urinary tract, they are in constant contact with a wide variety of cells, putting high demands on the communication skills of these cells. The purinergic signaling system offers a dynamic and versatile way for local and rapid intercellular communication and involves three processes: nucleotide release, enzymatic degradation, and activation of purinergic receptors. With an impressive number of molecular members of the system (15 P2 receptor subtypes and in total 16 nucleotide-degrading enzymes), cells have managed to put purines and pyrimidines as well as their derivatives to use in an array of different areas, including regulation of flow, secretion, and vascular tone. Indeed, the purinergic signaling system is an ancient way of intercellular communication that most likely could be found in the first most primitive life form [1]. The scope of this review is to give an overview of exciting features of purinergic signaling and examples of gaps to fill in understanding its role in the cells lining the body-the endothelium and the epithelium. Purinergic signaling-an overviewExtracellular nucleotides exert their paracrine signaling by binding to P2 receptors present at the cell surface. The P2 receptor family is divided into two groups: P2X receptors, which are ligand-activated ion channels, and P2Y receptors, which are G protein-coupled receptors (reviewed in [2]). Each receptor is characterized by its affinity pattern for different nucleotides and different cell types display varying receptor profiles. While P2X receptors respond only to ATP, P2Y receptors can be activated by other nucleotides such as ADP, UTP, and UDP. Extracellular nucleotide concentrations are precisely regulated by ecto-enzymes, which cleave nucleotide tri-/diphosphates. The result of signaling by the extracellular nucleotides ATP/ADP, UTP/UDP and the nucleoside adenosine is both acute, for example the rapid platelet aggregation induced by ADP, and chronic, via changes in gene expression induced by P2 receptor stimulation. Ligand availability for P2 receptors is regulated by a group of enzymes termed ectonucleotidases. NTPDase1 (apyrase; CD39) cleaves ATP to AMP, NTPDase2 (CD39L1) cleaves ATP to ADP, and 5′-ectonucleotidase (CD73) generates adenosine from AMP. Adenosine is the end product of purinergic signaling, acting on adenosine receptors (A1, A2a, A2b, and A3; also termed P1 receptors) or recycling by the cell after reuptake through the equilibrating nucleoside transporters ENT1 and 2. UTP is believed to be released simultaneously with ATP via the same mechanism but at a lower concentration (UTP/ATP, 1:10-100). UTP is degraded in the same way as ATP, but the biological function of uridine is poorly understood and no uridine receptor has been identified. Figure 1 shows an outline of nucleotide metabolism. Purinergic toneAll investigators that have tried t...

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P2X₄ receptors mediate ATP-induced calcium influx in human vascular endothelial cells

Cited by 177 publications

References 22 publications

Pannexin 1 in erythrocytes: Function without a gap

Pannexin 1 in erythrocytes: Function without a gap

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

The touching story of purinergic signaling in epithelial and endothelial cells

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P2X4 receptors mediate ATP-induced calcium influx in human vascular endothelial cells

Cited by 177 publications

References 22 publications

Pannexin 1 in erythrocytes: Function without a gap

Pannexin 1 in erythrocytes: Function without a gap

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

The touching story of purinergic signaling in epithelial and endothelial cells

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P2X₄ receptors mediate ATP-induced calcium influx in human vascular endothelial cells