Ca2+ entry following P2X receptor activation induces IP3 receptor‐mediated Ca2+ release in myocytes from small renal arteries

Povstyan, Oleksandr V.; Harhun, Maksym I.; Gordienko, Dmitri

doi:10.1111/j.1476-5381.2010.01169.x

Cited by 31 publications

(25 citation statements)

References 98 publications

(242 reference statements)

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“…3b). As previously shown in animal studies [26], repetitive applications of 10 μmol/l αβ-meATP induced response desensitisation. In our experiments, 10 μmol/l αβ-meATP-mediated increases in [Ca 2+ ] i showed near complete recovery following a 20-min interval between applications, with a mean normalised peak fluorescence (Fig.…”

Section: +supporting

confidence: 53%

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Nichols

Povstyan

Albert

et al. 2014

Purinergic Signalling

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Stimulation of P2X receptors by ATP in vascular smooth muscle cells (VSMCs) is proposed to mediate vascular tone. However, understanding of P2X receptor-mediated actions in human blood vessels is limited, and therefore, the current work investigates the role of P2X receptors in freshly isolated small human gastro-omental arteries (HGOAs). Expression of P2X1 and P2X4 receptor subunit messenger RNA (mRNA) and protein was identified in individual HGOA VSMCs using RT-PCR and immunofluorescent analysis and using Western blot in multi-cellular preparations. ATP of 10 μmol/l and αβ-meATP of 10 μmol/l, a selective P2X receptor agonist, evoked robust increases in [Ca 2+ ] i in fluo-3-loaded HGOA VSMCs. Pre-incubation with 1 μmol/l NF279, a selective P2X receptor antagonist, reduced the amplitude of αβ-meATP-induced increase in [Ca 2+ ] i by about 70 %. ATP of 10 μmol/l and αβ-meATP of 10 μmol/l produced similar contractile responses in segments of HGOA, and these contractions were greatly reduced by 2 μmol/l NF449, a selective P2X receptor inhibitor. These data suggest that VSMCs from HGOA express P2X1 and P2X4 receptor subunits with homomeric P2X1 receptors likely serving as the predominant target for extracellular ATP.

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Section: +supporting

confidence: 53%

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Nichols

Povstyan

Albert

et al. 2014

Purinergic Signalling

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“…ATP, adenosine, and other endogenous agents can activate vasoconstrictor purinergic homomeric P 2 X 1 , heteromeric P 2 X 1/4 , or adenosine A 1 receptors, respectively, on preglomerular VSMCs (521,565,1510,1540). Activation of P 2 X receptors by ATP induced ligand-gated cation influx, membrane depolarization, and Ca 2ϩ entry via VOCCs that were reinforced by inositol trisphosphate (IP 3 ) receptor-mediated Ca 2ϩ mobilization (565,683,685,1197). Studies examining the potential role of P 2 X receptors in renal autoregulation, in particular MD-TGF responses in different nephron populations, have yielded conflicting results.…”

Section: Conventional Macula Densa Tubuloglomerular Feedbackmentioning

confidence: 99%

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

391

383

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Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

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“…Taken together, the data suggest that P2X7R stimulation led to IP3R-mediated Ca 2þ release, Ca 2þ store depletion, ER stress and eventually apoptotic cell death (see schematic diagram in Fig. 8 [Povstyan et al, 2011]. In human fetal astrocytes, influx of Ca 2þ via P2 purinoceptors activated by di(adenosine-5 0 ) pentaphosphate causes Ca 2þ release through both IP3R and RYR [Holden et al, 2000].…”

Section: Discussionmentioning

confidence: 82%

Ca²⁺ store depletion and endoplasmic reticulum stress are involved in P2X7 receptor‐mediated neurotoxicity in differentiated NG108‐15 cells

Chao

Huang

et al. 2012

J of Cellular Biochemistry

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P2X7 receptor (P2X7R) activation by extracellular ATP triggers influx of Na(+) and Ca(2+), cytosolic Ca(2+) overload and consequently cytotoxicity. Whether disturbances in endoplasmic reticulum (ER) Ca(2+) homeostasis and ER stress are involved in P2X7R-mediated cell death is unknown. In this study, a P2X7R agonist (BzATP) was used to activate P2X7R in differentiated NG108-15 neuronal cells. In a concentration-dependent manner, application of BzATP (10-100 µM) immediately raised cytosolic Ca(2+) concentration ([Ca(2+)]i) and caused cell death after a 24-h incubation. P2X7R activation for 2 h did not cause cell death but resulted in a sustained reduction in ER Ca2+ pool size, as evidenced by a diminished cyclopiazonic acid-induced Ca(2+) discharge (fura 2 assay) and a lower fluorescent signal in cells loaded with Mag-fura 2 (ER-specific Ca(2+)-fluorescent dye). Furthermore, P2X7R activation (2 h) led to the appearance of markers of ER stress [phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α) and C/EBP homologous protein (CHOP)] and apoptosis (cleaved caspase 3). Xestospongin C (XeC), an antagonist of inositol-1,4,5-trisphosphate (IP3) receptor (IP3R), strongly inhibited BzATP-triggered [Ca(2+)]i elevation, suggesting that the latter involved Ca(2+) release via IP3R. XeC pretreatment not only attenuated the reduction in Ca(2+) pool size in BzATP-treated cells, but also rescued cell death and prevented BzATP-induced appearance of ER stress and apoptotic markers. These novel observations suggest that P2X7R activation caused not only Ca(2+) overload, but also Ca(2+) release via IP3R, sustained Ca(2+) store depletion, ER stress and eventually apoptotic cell death.

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Ca²⁺ entry following P2X receptor activation induces IP₃ receptor‐mediated Ca²⁺ release in myocytes from small renal arteries

Cited by 31 publications

References 98 publications

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Renal Autoregulation in Health and Disease

Ca²⁺ store depletion and endoplasmic reticulum stress are involved in P2X7 receptor‐mediated neurotoxicity in differentiated NG108‐15 cells

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Ca2+ entry following P2X receptor activation induces IP3 receptor‐mediated Ca2+ release in myocytes from small renal arteries

Cited by 31 publications

References 98 publications

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Renal Autoregulation in Health and Disease

Ca2+ store depletion and endoplasmic reticulum stress are involved in P2X7 receptor‐mediated neurotoxicity in differentiated NG108‐15 cells

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Ca²⁺ entry following P2X receptor activation induces IP₃ receptor‐mediated Ca²⁺ release in myocytes from small renal arteries

Ca²⁺ store depletion and endoplasmic reticulum stress are involved in P2X7 receptor‐mediated neurotoxicity in differentiated NG108‐15 cells