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P2Y1 receptor in Alzheimer’s disease

Neural Regeneration Research 2025年第2期20卷 440-453页

作者： Shan Luo Yifei Wang Tatsuhiro Hisatsune Department of Integrated Biosciences The University of TokyoKashiwaJapan

Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated *** amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last ***,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic *** evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s *** receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s *** review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.

关键词： astrocytes neuroinflammation P2Y1 receptor purinergic receptor

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purinergic receptors in Basal Ganglia Diseases:Shared Molecular Mechanisms between Huntington’s and Parkinson’s Disease

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Neuroscience Bulletin 2020年第11期36卷 1299-1314页

作者： Talita Glaser Roberta Andrejew Agatha Oliveira-Giacomelli Deidiane Elisa Ribeiro Lucas Bonfim Marques Qing Ye Wen-Jing Ren Alexey Semyanov Peter Illes Yong Tang Henning Ulrich Department of Biochemistry Institute of ChemistryUniversity of Sao PauloAv.Prof.Lineu Prestes 74&Sao PauloSP 05508-000Brazil Key Laboratory of Sichuan Province for Acupuncture and Chronobiology Chengdu 610075China Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesMoscow 117997Russia Sechenov First Moscow State Medical University Moscow 119992Russia Rudolf-Boehm-Institut ftir Pharmakologie und Toxikologie Universitat LeipzigLeipzig 04107Germany International Collaborative Centre on Big Science Plan for Purine Signaling Chengdu University of Traditional Chinese MedicineChengdu 610075China

Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,*** review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative *** adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor ***,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor *** interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal ***,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD.

关键词： purinergic receptor Central nervous system Huntington’s disease Parkinson’s disease 6-hydroxydopamine

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Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation

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Neuroscience Bulletin 2022年第4期38卷 359-372页

作者： Yan-Yan Wu Hai-Long Zhang Xiaomin Lu Han Du Yong-Chang Li Ping-An Zhang Guang-Yin Xu Jiangsu Key Laboratory of Neuropsychiatric Diseases Institute of NeuroscienceSoochow UniversitySuzhou 215123China Department of Oncology The Affiliated Haian Hospital of Nantong UniversityNantong 226600China Center for Translational Medicine The Affiliated Zhangjiagang Hospital of Soochow UniversitySuzhou 215600China

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread,chronic abdominal pain associated with altered bowel *** amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal *** this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1(GATA1)in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation(NCI).The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay,chromatin immunoprecipitation,patch clamp,and interference in vitro and in *** addition,a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG *** showed that NCI caused the induction of GATA1,Ten-eleven translocation 3(TET3),and purinergic receptors(P2X7Rs)in astrocytes of the spinal dorsal horn,and demonstrated that inhibiting these molecules markedly increased the pain threshold,inhibited the activation of astrocytes,and decreased the spinal sEPSC *** also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1–TET3 physical interaction and GATA1 binding at the p2x7r ***,we showed that demethylation of the p2x7r locus(and the attendant increase in P2X7R expression)was reversed upon knockdown of GATA1 or TET3 expression,and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r *** results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r trans

关键词： Chronic visceral pain GATA binding protein 1 Ten-eleven translocation 3 purinergic receptor Epigenetic regulation Spinal astrocytes

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Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine

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Acta Pharmacologica Sinica 2006年第8期27卷 1085-1092页

作者： Ming-xia WANG~2 Lei-ming REN~3 ~2The Fourth Affiliated Hospital,Hebei Medical University,Shijiazhuang 050011,China,~3School of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China The Fourth Affiliated Hospital Hebei Medical University Shijiazhuang China School of Pharmacy Hebei Medical University Shijiazhuang China

Aim:To study the growth inhibitory and apoptotic effects of adenosine triphos-phate(ATP)and adenosine(ADO)on human gastric carcinoma(HGC)-27 cells invitro and the mechanisms related to the actions of ATP and ***:MTTassay was used to determine the reduction of cell *** morphologicalchanges of HGC-27 cells induced by ATP or ADO were observed under fluores-cence light microscope by acridine orange/ethidium bromide double-stained *** internucleosomal fragmentation of genomic DNA was detected by agarosegel *** apoptotic rate and cell-cycle analysis after treatmentwith ATP or ADO was determined by flow ***:ATP,ADO and theintermediate metabolites,ADP and AMP,and the agonist of purinergic receptors,reduced cell viability of HGC-27 cells at doses of 0.3 and 1.0 mmol·*** distri-bution of cell cycle phase and proliferation index(PI)value of HGC-27 cells changedwhen exposed to ATP or ADO at the concentrations of 0.1,0.3 and 1 mmol/L for *** and ADO both altered the distribution of cell cycle phase via G0/G1-phasearrest and significantly decreased PI *** light microscope,the tumorcells exposed to 0.3 mmol·L-1ATP or ADO displayed morphological changes ofapoptosis;a ladder-like pattern of DNA fragmentation obtained from HGC-27 cellstreated with 0.1-1 mmol·L-1ATP or ADO appeared in agarose gel electrophoresis;ATP and ADO induced the apoptosis of HGC-27 ceils in a dose-dependent man-ner at concentrations between 0.03-1 *** maximum apoptotic rate ofHGC-27 cells exposed to ATP or ADO for 48 h was 13.53% or 15.9%,***-27 cell death induced by ATP or ADO was significantly inhibited by dipy-ridamole(10 mmol.L-1),an inhibitor of adenosine transporter,but was not affectedby aminophylline,a broad inhibitor of P1 receptors and pyridoxal-phosphate-6-azophenyl-2,4-disulphonic acid tetrasodium salt(30 μmol.L-1),a non-selectiveantagonist of P2 ***:Extracellular ATP and ADO reduced thecell

关键词： apoptosis adenosine triphosphate adenosine gastric carcinoma cells purinergic receptor

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The role of P2Y1 purinergic receptors in regulation of vasopressin and oxytocin release from the neurohypothysis

The role of P2Y1 purinergic receptors in regulation of vasop...

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2008北京国际生理科学学术大会

作者： GOMES Dayane A STEVENS Wanida SLADEK Celia D Department of Physiology and Biophysics University of Colorado Denver Health Sciences CenterAuroraCOUSA

ATP and phenylephrine(PE,α1 adrenergic receptor agonist)co-applied to explants of the hypothalamoneurohypophyseal system(HNS)act synergistically to stimulate vasopressin and oxytocin release and generate an extended elevation in intracellular calcium([Ca])in supraoptic nucleus neurons(SON).Both P2X and P2Y purinergic receptors contribute to the ATP-induced increase in[Ca] in *** immunohistochemical and immuno-blotting studies revealed the existence of P2Y1 purinergic receptors(P2Y1R)proteins in ***, the functional role of P2YlRs in regulation of vasopressin(VP)and oxytocin(OT)release was evaluated by studies perfusing the HNS *** of P2Y1Rs by the specific agonist 2-Methyl-thio-ADP significantly increased VP release from HNS explants compared to *** the other hand,exposure to the specific P2Y1R antagonist,MRS2179,suppressed the ATP+PE stimulated synergistic VP release from the HNS *** results were obtained for OT *** findings strongly support an essential role for P2Y1Rs in regulating VP and OT hormone release from *** studies are ongoing to clarify the mechanisms underlying the regulation of VP and OT release by P2YRs.

关键词： purinergic receptor vasopressin supraoptic nucleus ATP

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