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P2Y2 receptor

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https://www.readbyqxmd.com/read/28332205/evidence-that-5-ht-stimulates-intracellular-ca-2-signalling-and-activates-pannexin-1-currents-in-type-ii-cells-of-the-rat-carotid-body
#1
Sindhubarathi Murali, Min Zhang, Colin A Nurse
Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-hydroxytryptamine (5-HT) and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca(2+) ]i ) and activating carbenoxolone-sensitive, ATP-permeable, pannexin-1 (Panx-1)-like channels. Here, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca(2+) ]i responses in a subpopulation of type I cells, and in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28322086/viability-of-sh-sy5y-cells-is-associated-with-purinergic-p2-receptor-expression-alterations
#2
Arda Örçen, Vuslat Yilmaz, Murat Giriş, Uğur Akcan, Erdem Tüzün, Gaye Erten
To investigate the role of metabotrophic purinergic P2Y receptors in neuroblastoma cell survival, expression of P2 receptors by normal mouse (C57BL/6) brain and human neuroblastoma SH-SY5Y cells was investigated by Western blot and real time PCR studies. Viability of SH-SY5Y cells treated with purinergic receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) was evaluated by MTT assay and flow cytometry. In the brain samples of C57BL/6 mice, expressions of P2Y4 and P2X7 were significantly reduced, whereas that of P2Y1 was significantly elevated in an age-dependent manner...
March 2017: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/28209512/n-glycan-dependent-cell-surface-expression-of-the-p2y2-receptor-and-n-glycan-independent-distribution-to-lipid-rafts
#3
Tetsuto Nakagawa, Chihiro Takahashi, Hitomi Matsuzaki, Shohei Takeyama, Shinpei Sato, Ayaka Sato, Yoshiyuki Kuroda, Hideyoshi Higashi
P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. P2Y2R is involved in pain, proinflammatory changes, and blood pressure control. Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188289/human-keratinocytes-respond-to-extracellular-utp-by-induction-of-hyaluronan-synthase-2-expression-and-increased-hyaluronan-synthesis
#4
Tiina A Jokela, Riikka Kärnä, Leena Rauhala, Genevieve Bart, Sanna Pasonen-Seppänen, Sanna Oikari, Markku I Tammi, Raija H Tammi
The release of nucleotides into extracellular space is triggered by insults like wounding and ultraviolet radiation, resulting in stimulatory or inhibitory signals via plasma membrane nucleotide receptors. As similar insults are known to activate hyaluronan synthesis we explored the possibility that extracellular UTP or its breakdown products UDP and UMP act as mediators for hyaluronan synthase (HAS) activation in human epidermal keratinocytes. UTP increased hyaluronan both in the pericellular matrix and in the culture medium of HaCaT cells...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28128420/grk2-desensitizes-flow-induced-responses-in-osteoblasts
#5
Y Xing, Y Gu, X Shan, L Wang, J You
Bone desensitization after mechanical loading is essential for bone to adapt to its mechanical environment. However, the desensitization mechanism is unknown. Previous studies suggest that G protein-coupled receptors (GPCRs), including P2Y and parathyroid hormone receptors, play important roles in osteoblast mechanobiology. Thus, for the present research, we examined the role of G protein-coupled receptor kinase 2 (GRK2) in osteoblast desensitization after exposure to mechanical stimulation. We first showed the existence of osteoblast desensitization after mechanical stimulation based on cytosol Ca(2+) and phosphorylated ERK1/2 activities, detected using a fluorescent Ca(2+)-sensitive dye and western blotting, respectively...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28038380/the-p2y2-nucleotide-receptor-is-an-inhibitor-of-vascular-calcification
#6
Shaomin Qian, Jenna N Regan, Maxwell T Shelton, April Hoggatt, Khalid S Mohammad, Paul B Herring, Cheikh I Seye
BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE(-/-)P2Y2R(-/-)) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo...
February 2017: Atherosclerosis
https://www.readbyqxmd.com/read/27977904/adenosine-triphosphate-induces-p2y2-activation-and-il-8-release-in-human-esophageal-epithelial-cells
#7
Liping Wu, Tadayuki Oshima, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
BACKGROUND AND AIM: Immune-mediated mucosal inflammation characterized by the release of IL-8 is associated with gastroesophageal reflux disease (GERD). ATP released by human esophageal epithelial cells mediates the release of cytokines through P2 nucleotide receptors that are present on various cells, including human esophageal epithelial cells. This study characterized and identified human esophageal epithelial P2 receptors that are responsible for ATP-mediated release of IL-8 by using a human esophageal stratified squamous epithelial model...
December 15, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#8
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#9
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27856454/endothelial-cell-specific-deletion-of-p2y2-receptor-promotes-plaque-stability-in-atherosclerosis-susceptible-apoe-null-mice
#10
Xingjuan Chen, Shaomin Qian, April Hoggatt, Hongying Tang, Timothy A Hacker, Alexander G Obukhov, Paul B Herring, Cheikh I Seye
OBJECTIVE: Nucleotide P2Y2 receptor (P2Y2R) contributes to vascular inflammation by increasing vascular cell adhesion molecule-1 expression in endothelial cells (EC), and global P2Y2R deficiency prevents fatty streak formation in apolipoprotein E null (ApoE(-/-)) mice. Because P2Y2R is ubiquitously expressed in vascular cells, we investigated the contribution of endothelial P2Y2R in the pathogenesis of atherosclerosis. APPROACH AND RESULTS: EC-specific P2Y2R-deficient mice were generated by breeding VEcadherin5-Cre mice with the P2Y2R floxed mice...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856358/p2x7rs-are-involved-in-cell-death-growth-and-cellular-signaling-in-primary-human-osteoblasts
#11
Ankita Agrawal, Zanne Henriksen, Susanne Syberg, Solveig Petersen, Derya Aslan, Marie Solgaard, Nis Nissen, Tommy Korsgaard Larsen, Peter Schwarz, Thomas H Steinberg, Niklas Rye Jørgensen
The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling...
February 2017: Bone
https://www.readbyqxmd.com/read/27818661/the-role-of-purine-metabolites-as-damps-in-acute-graft-versus-host-disease
#12
REVIEW
Petya Apostolova, Robert Zeiser
Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27807254/upregulation-of-p2y2-nucleotide-receptor-in-human-hepatocellular-carcinoma-cells
#13
Eunyoung Tak, Dae Young Jun, Seok-Hwan Kim, Gil-Chun Park, Jooyoung Lee, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Objective To examine if hypoxia inducible factor-1α (HIF-1α) can induce the upregulation of the purinergic receptor P2Y2 (P2Y2) and thereby promote the viability of human hepatocellular carcinoma (HCC) cells under hypoxic conditions. Methods Archival HCC tumour specimens and corresponding non-cancerous tissues were examined immunohistochemically for P2Y2 protein. A series of in vitro experiments were undertaken using HCC cell lines to determine the effect of hypoxia on HIF-1α and P2Y2 levels, the effect of HIF-1α upregulation on P2Y2 levels, and the effect of P2Y2 upregulation on cell viability under hypoxic conditions...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27797339/endothelial-cation-channel-piezo1-controls-blood-pressure-by-mediating-flow-induced-atp-release
#14
ShengPeng Wang, Ramesh Chennupati, Harmandeep Kaur, Andras Iring, Nina Wettschureck, Stefan Offermanns
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27768902/regulation-of-proteasome-activity-by-p2y2-receptor-underlies-the-neuroprotective-effects-of-extracellular-nucleotides
#15
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27766552/synthesis-characterization-and-in-vitro-evaluation-of-the-selective-p2y2-receptor-antagonist-ar-c118925
#16
Muhammad Rafehi, Joachim C Burbiel, Isaac Y Attah, Aliaa Abdelrahman, Christa E Müller
The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27761681/diadenosine-tetraphosphate-ap4a-inhibits-atp-induced-excitotoxicity-a-neuroprotective-strategy-for-traumatic-spinal-cord-injury-treatment
#17
David Reigada, Rosa María Navarro-Ruiz, Marcos Javier Caballero-López, Ángela Del Águila, Teresa Muñoz-Galdeano, Rodrigo M Maza, Manuel Nieto-Díaz
Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap4A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27755650/adp-induced-ca-2-signaling-and-proliferation-of-rat-ventricular-myofibroblasts-depend-on-phospholipase-c-linked-trp-channels-activation-within-lipid-rafts
#18
Mariana Certal, Adriana Vinhas, Aurora Barros-Barbosa, Fátima Ferreirinha, Maria Adelina Costa, Paulo Correia-de-Sá
Nucleotides released during heart injury affect myocardium electrophysiology and remodeling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca(2+) ]i accumulation and growth of DDR-2/α-SMA-expressing myofibroblasts from adult rat ventricles via P2Y4 and P2Y2 receptors activation, respectively. Ventricular myofibroblasts also express ADP-sensitive P2Y1 , P2Y12 , and P2Y13 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells...
June 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27723650/direct-evidence-for-p2y2-receptor-involvement-in-vascular-response-to-injury
#19
Yuksel Agca, Shaomin Qian, Cansu Agca, Cheikh I Seye
OBJECTIVES: Extracellular nucleotide release at the site of arterial injury mediates the proliferation and migration of vascular smooth muscle cells. Our aim was to investigate the role of the P2Y2 nucleotide receptor (P2Y2R) in neointimal hyperplasia. Approach and Results: Vascular injury was induced by the implantation of a polyethylene cuff around the femoral artery in wild-type and P2Y2R-deficient mice (P2Y2R-/-). Electron microscopy was used to analyze monocyte and lymphocyte influx to the intima 36 h after injury...
2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27709366/erratum-to-p2y1-p2y2-and-trpv1-receptors-are-increased-in-diarrhea-predominant-irritable-bowel-syndrome-and-p2y2-correlates-with-abdominal-pain
#20
Yumei Luo, Cheng Feng, Jing Wu, Yongxing Wu, Dong Liu, Jie Wu, Fei Dai, Jun Zhang
No abstract text is available yet for this article.
October 5, 2016: Digestive Diseases and Sciences
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