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Zhenhua Ji, Yuting Xie, Yu Guan, Yujian Zhang, Kin-Sang Cho, Min Ji, Yongping You
Previous studies have demonstrated that activation of P2X7 receptors (P2X7 R) results in the proliferation and migration of some types of tumor. Here, we asked whether and how the activated P2X7 R contribute to proliferation and migration of human glioma cells. Results showed that the number of P2X7 R positive cells was increasing with grade of tumor. In U87 and U251 human glioma cell lines, both expressed P2X7 R and the expression was enhanced by 3'-O-(4-benzoylbenzoyl) ATP (BzATP), the agonist of P2X7 R, and siRNA...
2018: BioMed Research International
A M Rodrigues, R S Serralha, C Farias, G R Punaro, M J S Fernandes, Elisa Mieko Suemitsu Higa
Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats...
March 14, 2018: Purinergic Signalling
Ivana Novak, Anna Solini
Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines...
March 6, 2018: Current Opinion in Immunology
Bieneke Janssen, Danielle J Vugts, Albert D Windhorst, Robert H Mach
Neuroinflammation, which involves microglial activation, is thought to play a key role in the development and progression of neurodegenerative diseases and other brain pathologies. Positron emission tomography is an ideal imaging technique for studying biochemical processes in vivo, and particularly for studying the living brain. Neuroinflammation has been traditionally studied using radiotracers targeting the translocator protein 18 kDa, but this comes with certain limitations. The current review describes alternative biological targets that have gained interest for the imaging of microglial activation over recent years, such as the cannabinoid receptor type 2, cyclooxygenase-2, the P2X₇ receptor and reactive oxygen species, and some promising radiotracers for these targets...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Naoki Wada, Takahiro Shimizu, Nobutaka Shimizu, William C de Groat, Anthony J Kanai, Pradeep Tyagi, Hidehiro Kakizaki, Naoki Yoshimura
AIMS: To investigate the role of nerve growth factor (NGF) in lower urinary tract dysfunction in mice with spinal cord injury (SCI). METHODS: Using 4-week SCI mice, single-filling cystometry and external urethral sphincter (EUS)-electromyography were performed under an awake condition. In some SCI mice, anti-NGF antibodies (10 µg/kg/h) were administered for 1 or 2 weeks before the urodynamic study. NGF levels in the bladder and L6/S1 spinal cord were assayed by ELISA...
March 8, 2018: Neurourology and Urodynamics
J Wang-Fang, J Chun-Jie, G Fei, L Jia-Hui, L Ming
ATP (Adenosine triphosphate) is an important endogenous damage - associated molecular pattern (DAMP). P2X7 R is an ATP-gated cation channel. ATP-P2X7 R plays a vital role in the pathophysiology of many diseases because P2X7 R is distributed on various immune cells. ATP-P2X7 R signal transduction pathway has been implicated to participate in the body's immune defense against pathogens. This paper reviews the recent progress regarding ATP-P2X7 R and its effects on parasitic diseases.
July 24, 2017: Zhongguo Xue Xi Chong Bing Fang Zhi za Zhi, Chinese Journal of Schistosomiasis Control
Sheraz Khoja, Nhat Huynh, Alicia M P Warnecke, Liana Asatryan, Michael W Jakowec, Daryl L Davies
The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs. Avermectins are derived by fermentation of soil micro-organism, Streptomyces avermitilis, and have been extensively used for treatment of parasitic infections...
March 2, 2018: Psychopharmacology
Nishkantha Arulkumaran, Marije L Sixma, Sean Pollen, Elias Ceravola, Elisa Jentho, Maria Prendecki, Paul S Bass, Frederick W K Tam, Robert J Unwin, Mervyn Singer
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis...
March 2018: Physiological Reports
Carmen Fotino, Diego Dal Ben, Elena Adinolfi
BACKGROUND: Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the generation, recognition and degradation of extracellular ATP and adenosine. The main actors of this system include P2X, P2Y and Adenosine Receptors, ectonucleotidases CD39 and CD73 and Adenosine Deaminase. The purinergic network recently emerged as a central player in several physiopathological conditions particularly those linked to immune system regulation including type 1 and type 2 diabetes...
February 26, 2018: Medicinal Chemistry
Sheraz Khoja, Nhat Huynh, Liana Asatryan, Michael W Jakowec, Daryl L Davies
Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ionotropic receptors that are gated by adenosine 5'-triphosphate (ATP). Accumulating evidence indicates that P2X4Rs play an important role in regulation of ethanol intake. At the molecular level, ethanol's inhibitory effects on P2X4Rs are antagonized by ivermectin (IVM), in part, via action on P2X4Rs. Behaviorally, male mice deficient in the p2rx4 gene (P2X4R knockout [KO]) have been shown to exhibit a transient increase in ethanol intake over a period of 4 days, as demonstrated by social and binge drinking paradigms...
September 30, 2017: Alcohol
Luiz E B Savio, Paola de Andrade Mello, Cleide Gonçalves da Silva, Robson Coutinho-Silva
Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors-P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels)...
2018: Frontiers in Pharmacology
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
Linyu Wei, Sharifah A Syed Mortadza, Jing Yan, Libin Zhang, Lu Wang, Yaling Yin, Chaokun Li, Sylvie Chalon, Patrick Emond, Catherine Belzung, Dongliang Li, Chengbiao Lu, Sebastien Roger, Lin-Hua Jiang
Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response...
February 14, 2018: Neuroscience and Biobehavioral Reviews
Megumi Hanaka, Kousuke Iba, Takayuki Dohke, Kumiko Kanaya, Shunichiro Okazaki, Toshihiko Yamashita
Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice...
February 14, 2018: Bone
Francesco Di Virgilio, Anna L Giuliani, Valentina Vultaggio-Poma, Simonetta Falzoni, Alba C Sarti
The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD + covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation...
2018: Frontiers in Pharmacology
Fernanda C Cardoso, Mahadhi Hasan, Tianjiao Zhao, Richard J Lewis
PURPOSE OF REVIEW: Pain is a distressing protective sensory experience warning of actual or potential tissue damage. Natural toxins have evolved to exploit pain and related neuronal pathways to facilitate prey capture and for defence, often producing either numbness, paralysis or intense pain by selectively modulating ion channels and receptors in pain pathways. Understanding how toxins modulate pain pathways can enhance our understanding of the physiological and pathological basis of pain...
February 12, 2018: Current Opinion in Supportive and Palliative Care
Cheng-Long Liu, Ze-Yu Deng, Er-Rong Du, Chang-Shui Xu
Purinergic signaling contributes to inflammatory and immune responses. The activation of the P2X purinoceptor 7 (P2X7) in satellite glial cells (SGCs) may be an essential component in the promotion of inflammation and neuropathic pain. Long non‑coding RNAs (lncRNAs) are involved in multiple physiological and pathological processes. The aim of the present study was to investigate the effects of a small interfering RNA for the lncRNA BC168687 on SGC P2X7 expression in a high glucose and high free fatty acids (HGHF) environment...
February 13, 2018: Molecular Medicine Reports
Chou-Ming Yeh, Yu-Jung Lin, Tien-Huan Hsu, Ting Ruan
Reactive oxygen species may induce hypersensitivity of vagal lung C-fibers (VLCFs) through the interaction of TRPA1 and P2X receptors. Genistein is a soy-derived isoflavone that exerts antioxidant effects by binding to estrogen receptors (ERs), ERα and ERβ. We investigated whether ER activation by genistein can suppress H₂O₂-mediated VLCF hypersensitivity and identified the types of ERs involved. Results revealed that subcutaneous injection of genistein or PPT (a selective ERα agonist) can attenuate H₂O₂-induced VLCF hypersensitivity...
January 29, 2018: Chinese Journal of Physiology
Tsuyoshi Yoshizawa, Yukio Hayashi, Akira Yoshida, Shohei Yoshida, Yoshihiko Ito, Kenya Yamaguchi, Shizuo Yamada, Satoru Takahashi
OBJECTIVES: To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P2X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes...
January 24, 2018: International Urology and Nephrology
Jing Liu, Ningning Li, Ruofan Sheng, Rui Wang, Zude Xu, Ying Mao, Yin Wang, Ying Liu
The present study investigated the altered expression of p2X purinoceptor (P2X7 R) in astrocytoma. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the P2X7 R expression in glioblastoma (GBM) and surrounding normal brain tissue. DNA methylation levels of P2X7 R gene promoter in GBM were analyzed using a Sequenom MassARRAY® System. Immunohistochemistry (IHC) was used to detect the expression of P2X7 R in astrocytoma at different malignancy grades, including diffuse astrocytoma, anaplastic astrocytoma and GBM...
December 2017: Oncology Letters
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