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https://www.readbyqxmd.com/read/28326637/purinergic-receptors-p2rx4-and-p2rx7-in-familial-multiple-sclerosis
#1
A Dessa Sadovnick, Ben J Gu, Anthony L Traboulsee, Cecily Q Bernales, Mary Encarnacion, Irene M Yee, Maria G Criscuoli, Xin Huang, Amber Ou, Carol J Milligan, Steven Petrou, James S Wiley, Carles Vilariño-Güell
Genetic variants in the purinergic receptors P2RX4 and P2RX7 have been shown to affect susceptibility to multiple sclerosis (MS). In this study we set out to evaluate whether rare coding variants of major effect could also be identified in these purinergic receptors. Sequencing analysis of P2RX4 and P2RX7 in 193 MS patients and 100 controls led to the identification of a rare three variant haplotype (P2RX7 rs140915863:C>T (p.T205M), P2RX7 rs201921967:A>G (p.N361S) and P2RX4 rs765866317:G>A (p.G135S)) segregating with disease in a multi-incident family with six family members diagnosed with MS (LOD = 3...
March 21, 2017: Human Mutation
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/28318884/udp-p2y6-receptor-signaling-regulates-ige-dependent-degranulation-in-human-basophils
#3
Manabu Nakano, Koichi Ito, Takeo Yuno, Nobuyuki Soma, Syun Aburakawa, Kosuke Kasai, Toshiya Nakamura, Hideki Takami
BACKGROUND: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca(2+) release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils...
March 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28300322/astroglia-as-a-cellular-target-for-neuroprotection-and-treatment-of-neuro-psychiatric-disorders
#4
REVIEW
Beihui Liu, Anja G Teschemacher, Sergey Kasparov
Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem-cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28300164/role-of-purinergic-signaling-in-experimental-pneumococcal-meningitis
#5
Marco Zierhut, Susanne Dyckhoff, Ilias Masouris, Matthias Klein, Sven Hammerschmidt, Hans-Walter Pfister, Korcan Ayata, Marco Idzko, Uwe Koedel
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298636/the-purinergic-receptor-p2x5-regulates-inflammasome-activity-and-hyper-multinucleation-of-murine-osteoclasts
#6
Hyunsoo Kim, Matthew C Walsh, Noriko Takegahara, Sarah A Middleton, Hong-In Shin, Junhyong Kim, Yongwon Choi
Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295755/evidence-for-a-functional-vasoconstrictor-role-for-atp-in-the-human-cutaneous-microvasculature
#7
James A Lang, Alex C Krajek, Kevin A Smaller
Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, whereas the remainder is due to one or more unidentified coreleased sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis (MD) probes in forearm skin and whole-body cooling (Tsk  = 30...
March 10, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28285362/purinergic-ecto-enzymes-participate-in-the-thromboregulation-in-acute-in-mice-infection-by-trypanosoma-cruzi
#8
Guilherme M do Carmo, Pedro H Doleski, Mariângela F de Sá, Thirssa H Grando, Nathieli B Bottari, Daniela B R Leal, Lucas T Gressler, Ricardo E Mendes, Lenita M Stefani, Silvia G Monteiro, Aleksandro S Da Silva
Coagulation disorders have been described in Chagas disease with thrombocytopenia as an important event. Several mechanisms may be related to this pathogenesis, such as enzymes of the purinergic system, purine, and receptors involved in the regulation and modulation of physiological events related to hemostasis. Therefore, the aim of this study was to evaluate the activities of E-NTPDase, E-5'nucleotidase, and ecto-adenosine deaminase (E-ADA) in platelets of mice experimentally infected by Trypanosoma cruzi...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#9
REVIEW
Eliana Scemes, Jana Velíšková
It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28280061/purinergic-receptor-transactivation-by-the-%C3%AE-2-adrenergic-receptor-increases-intracellular-ca-2-in-non-excitable-cells
#10
Wayne Stallaert, Emma T van der Westhuizen, Anne-Marie Schonegge, Bianca Plouffe, Mireille Hogue, Viktoria Lukashova, Asuka Inoue, Satoru Ishida, Junken Aoki, Christian Le Gouill, Michel Bouvier
The β2 adrenergic receptor (β2AR) increases intracellular Ca(2+) in a variety of cell types. By combining pharmacological and genetic manipulations, we reveal a novel mechanism through which the β2AR promotes Ca(2+) mobilization (pEC50 = 7.32 ± 0.10) in non-excitable human embryonic kidney (HEK)-293S cells. Down-regulation of Gs with sustained cholera toxin pre-treatment and the use Gs-null HEK293 (ΔGs-HEK293) cells generated using the CRISPR/Cas9 system, combined with pharmacological modulation of cAMP formation revealed a Gs-dependent but cAMP-independent increase in intracellular Ca(2+) following β2AR stimulation...
March 9, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#11
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28279755/purinergic-p2-receptors-in-the-paraventricular-nucleus-of-the-hypothalamus-are-involved-in-hyperosmotic-induced-sympathoexcitation
#12
H C Ferreira-Neto, I M R Ribeiro, T S Moreira, S T Yao, V R Antunes
Increases in plasma osmolality activates the paraventricular nucleus of the hypothalamus (PVN) which in turn mounts a physiological response by increasing the release of arginine vasopressin and sympathetic nerve activity to end organs such as the kidney. The PVN expresses an abundance of purinergic receptors including P2X2 receptors. In the present study, we sought to determine 1) whether P2X2-expressing PVN neurons are activated by hypertonic saline or hypertonic mannitol and 2) what effects P2X receptor blockade has on sympathetic nerve activation mediated by a hyperosmotic stimulus...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28277742/mir-185-p2y6-axis-inhibits-angiotensin-ii-induced-human-aortic-vascular-smooth-muscle-cell-proliferation
#13
Shunmin Wang, Lujun Tang, Qian Zhou, Duomei Lu, Wulei Duan, Cheng Chen, Lu Huang, Yuansheng Tan
The abnormal proliferation and apoptosis of human aortic vascular smooth muscle cells (HAVSMCs) play an important role in the pathogenesis of hypertension. Recent study revealed that angiotensin II (Ang II) could elicit HAVSMC dysfunction, to induce or aggravate hypertension. Purinergic receptor P2Y6, an inflammation-inducible G protein-coupled receptor, promoted Ang II-induced hypertension. In the present study, we revealed that Ang II induced HAVSMC proliferation and upregulated P2Y6 protein levels. After knockdown of P2Y6, the promotive effect of Ang II on HAVSMC proliferation was restored...
March 9, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28275350/blockade-of-p2x4-receptors-inhibits-neuropathic-pain-related-behavior-by-preventing-mmp-9-activation-and-consequently-pronociceptive-interleukin-release-in-a-rat-model
#14
Agnieszka M Jurga, Anna Piotrowska, Wioletta Makuch, Barbara Przewlocka, Joanna Mika
Neuropathic pain is still an extremely important problem in today's medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, consequently, the levels of nociceptive interleukins after chronic constriction injury (CCI) of the right sciatic nerve, a rat model of neuropathic pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28274860/purinergic-2x7-receptor-nlrp3-pathway-triggers-neuronal-apoptosis-after-ischemic-stroke-in-the-mouse
#15
Xinchun Ye, Tong Shen, Jinxia Hu, Liang Zhang, Yunshan Zhang, Lei Bao, Chengcheng Cui, Guoliang Jin, Kun Zan, Zuohui Zhang, Xinxin Yang, Hongjuan Shi, Jie Zu, Ming Yu, Chengjie Song, Yulan Wang, Suhua Qi, Guiyun Cui
Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950)...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28265084/lys49-myotoxin-from-the-brazilian-lancehead-pit-viper-elicits-pain-through-regulated-atp-release
#16
Chuchu Zhang, Katalin F Medzihradszky, Elda E Sánchez, Allan I Basbaum, David Julius
Pain-producing animal venoms contain evolutionarily honed toxins that can be exploited to study and manipulate somatosensory and nociceptive signaling pathways. From a functional screen, we have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehead pit viper (Bothrops moojeni). BomoTx is closely related to a group of Lys49 myotoxins that have been shown to promote ATP release from myotubes through an unknown mechanism. Here we show that BomoTx excites a cohort of sensory neurons via ATP release and consequent activation of P2X2 and/or P2X3 purinergic receptors...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263802/abacavir-induces-platelet-endothelium-interactions-by-interfering-with-purinergic-signalling-a-step-from-inflammation-to-thrombosis
#17
Angeles Alvarez, Cesar Rios-Navarro, Maria Amparo Blanch-Ruiz, Victor Collado-Diaz, Isabel Andujar, Maria Angeles Martinez-Cuesta, Samuel Orden, Juan V Esplugues
The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway...
March 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28262230/placental-hemostasis-and-sterile-inflammation-new-insights-into-gestational-vascular-disease
#18
Shrey Kohli, Berend Isermann
Activation of the coagulation and inflammatory systems are physiologically occurring during pregnancy. However, excess activation of either system is well documented in gestational vascular diseases (GVD). GVD are placenta-mediated pregnancy complications and a major cause of feto-maternal morbidity and mortality. The causal relevance of excess coagulation and inflammatory responses for GVD remains largely unknown. Deciphering the causal relationship of excess coagulation and inflammation in GVD may allow conceptualizing new therapeutic approaches to combat GVD...
March 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28258700/the-ectonucleotidases-cd39-and-cd73-novel-checkpoint-inhibitor-targets
#19
REVIEW
Bertrand Allard, Maria Serena Longhi, Simon C Robson, John Stagg
Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are newly developing interventions that modify the patient's immune system to fight cancer, by either directly stimulating rejection-type processes or blocking suppressive pathways. Extracellular adenosine generated by the ectonucleotidases CD39 and CD73 is a newly recognized "immune checkpoint mediator" that interferes with anti-tumor immune responses...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28257945/effect-of-high-fat-diets-on-the-ntpdase-5-nucleotidase-and-acetylcholinesterase-activities-in-the-central-nervous-system
#20
Rosilene Rodrigues Kaizer, Rosélia Maria Spanevello, Eduarda Costa, Vera Maria Morsch, Maria Rosa Chitolina Schetinger
High fat diets are associated with the promotion of neurological diseases, such as Alzheimer disease (AD). This study aim investigate the high fat diets role to promotion of AD using as biochemistry parameter of status of central nervous system through the NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in brain of young rats. The intake of high fat diets promotes an inhibition of purinergic and cholinergic functions, mainly in the long-term exposure to saturated and saturated/unsaturated diets...
March 1, 2017: International Journal of Developmental Neuroscience
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