purinergic p2 receptors

Summary

Summary: A class of cell surface receptors for purines that prefer ATP or ADP over adenosine. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system. Subtypes have been proposed, usually designated P2 x, y, z, and t. P2x receptors may mediate fast synaptic transmission by ATP. The ADP-preferring P2t receptors in platelets stimulate aggregation.

Top Publications

  1. ncbi Molecular physiology of P2X receptors
    R Alan North
    Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield, United Kingdom
    Physiol Rev 82:1013-67. 2002
  2. ncbi Receptors for purines and pyrimidines
    V Ralevic
    School of Biomedical Sciences, Queen s Medical Centre, University of Nottingham, Nottingham, England
    Pharmacol Rev 50:413-92. 1998
  3. pmc Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor
    Pablo Pelegrin
    Department of Biomedical Science, University of Sheffield, Sheffield, UK
    EMBO J 25:5071-82. 2006
  4. ncbi Liaisons dangereuses: P2X(7) and the inflammasome
    Francesco Di Virgilio
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Via Borsari, 46, Ferrara, Italy
    Trends Pharmacol Sci 28:465-72. 2007
  5. pmc Crystal structure of the ATP-gated P2X(4) ion channel in the closed state
    Toshimitsu Kawate
    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA
    Nature 460:592-8. 2009
  6. ncbi Pharmacological profiles of cloned mammalian P2Y-receptor subtypes
    Ivar von Kügelgen
    Department of Pharmacology, University of Bonn, Reuterstrasse 2b, D 53113 Bonn, Germany
    Pharmacol Ther 110:415-32. 2006
  7. ncbi Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins
    Toshimitsu Kawate
    Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168 th Street, New York, New York 10032, USA
    Structure 14:673-81. 2006
  8. pmc ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way
    Alessandra Piccini
    Cell Biology Unit, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy
    Proc Natl Acad Sci U S A 105:8067-72. 2008
  9. pmc International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy
    Maria P Abbracchio
    Department of Pharmacological Sciences, University of Milan, Milan, Italy
    Pharmacol Rev 58:281-341. 2006
  10. ncbi Prasugrel versus clopidogrel in patients with acute coronary syndromes
    Stephen D Wiviott
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 357:2001-15. 2007

Detail Information

Publications278 found, 100 shown here

  1. ncbi Molecular physiology of P2X receptors
    R Alan North
    Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield, United Kingdom
    Physiol Rev 82:1013-67. 2002
    ..In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways...
  2. ncbi Receptors for purines and pyrimidines
    V Ralevic
    School of Biomedical Sciences, Queen s Medical Centre, University of Nottingham, Nottingham, England
    Pharmacol Rev 50:413-92. 1998
  3. pmc Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor
    Pablo Pelegrin
    Department of Biomedical Science, University of Sheffield, Sheffield, UK
    EMBO J 25:5071-82. 2006
    ....
  4. ncbi Liaisons dangereuses: P2X(7) and the inflammasome
    Francesco Di Virgilio
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Via Borsari, 46, Ferrara, Italy
    Trends Pharmacol Sci 28:465-72. 2007
    ....
  5. pmc Crystal structure of the ATP-gated P2X(4) ion channel in the closed state
    Toshimitsu Kawate
    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA
    Nature 460:592-8. 2009
    ..We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening...
  6. ncbi Pharmacological profiles of cloned mammalian P2Y-receptor subtypes
    Ivar von Kügelgen
    Department of Pharmacology, University of Bonn, Reuterstrasse 2b, D 53113 Bonn, Germany
    Pharmacol Ther 110:415-32. 2006
    ..Finally, UDP has been reported to act on receptors for cysteinyl leukotrienes as an additional agonist--indicating a dual agonist specificity of these receptors...
  7. ncbi Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins
    Toshimitsu Kawate
    Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168 th Street, New York, New York 10032, USA
    Structure 14:673-81. 2006
    ..We show the application of this precrystallization screening to four membrane proteins derived from prokaryotic or eukaryotic organisms...
  8. pmc ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way
    Alessandra Piccini
    Cell Biology Unit, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy
    Proc Natl Acad Sci U S A 105:8067-72. 2008
    ..Thus, stimuli acting on different pathogen-sensing receptors converge on a common pathway where ATP externalization is the first step in the cascade of events leading to inflammasome activation and IL-1beta and IL-18 secretion...
  9. pmc International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy
    Maria P Abbracchio
    Department of Pharmacological Sciences, University of Milan, Milan, Italy
    Pharmacol Rev 58:281-341. 2006
    ..These and other advances are discussed in the present review...
  10. ncbi Prasugrel versus clopidogrel in patients with acute coronary syndromes
    Stephen D Wiviott
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 357:2001-15. 2007
    ..Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention...
  11. pmc Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex
    Silviu Locovei
    Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA
    FEBS Lett 581:483-8. 2007
    ..Thus, pannexin1 appears to be the molecular substrate for the permeabilization pore (or death receptor channel) recruited into the P2X(7)R signaling complex...
  12. ncbi Nucleotide receptors: an emerging family of regulatory molecules in blood cells
    F Di Virgilio
    Department of Experimental and Diagnostic Medicine, Section of General Pathology and Medical Genetics, and Center of Biotechnology, University of Ferrara, Ferrara, Italy
    Blood 97:587-600. 2001
    ..These effects are mediated through a specific class of plasma membrane receptors called purinergic P2 receptors that, according to the molecular structure, are further subdivided into 2 subfamilies: P2Y and P2X...
  13. ncbi Purine and pyrimidine receptors
    G Burnstock
    Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, UK
    Cell Mol Life Sci 64:1471-83. 2007
    ..P2Y receptors are G protein-coupled receptors, and eight subtypes have been cloned and characterised to date...
  14. ncbi Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption
    Hua Zhu Ke
    Pfizer Global Research and Development, Groton Laboratories, Connecticut 06340, USA
    Mol Endocrinol 17:1356-67. 2003
    ..Thus, the P2X7 receptor represents a novel therapeutic target for the management of skeletal disorders such as osteoporosis...
  15. ncbi Pathophysiology and therapeutic potential of purinergic signaling
    Geoffrey Burnstock
    Autonomic Neuroscience Centre, Royal Free and University College Medical School, London NW3 2PF, UK
    Pharmacol Rev 58:58-86. 2006
    ..Recent advances in therapies using purinergic-related drugs in a wide range of pathological conditions will be addressed with speculation on future developments in the field...
  16. pmc Central role of the P2Y12 receptor in platelet activation
    Robert T Dorsam
    Department of Pharmacology, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA
    J Clin Invest 113:340-5. 2004
    ..The P2Y(12) receptor, activated by ADP, plays a central role in platelet activation and is the target of P2Y(12) receptor antagonists that have proven therapeutic value...
  17. ncbi Identification of the platelet ADP receptor targeted by antithrombotic drugs
    G Hollopeter
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA
    Nature 409:202-7. 2001
    ..Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases...
  18. ncbi Cellular distribution and functions of P2 receptor subtypes in different systems
    Geoffrey Burnstock
    Autonomic Neuroscience Institute, Royal Free and University College Medical School, London NW3 2PF, United Kingdom
    Int Rev Cytol 240:31-304. 2004
    ..Finally, there is some discussion of possible future developments in the purinergic signaling field...
  19. ncbi Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons
    Guang Yin Xu
    Marine Biomedical Institute and Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555 1069, USA
    J Neurosci 22:93-102. 2002
    ..These results suggest that P2X receptors are useful targets for inflammatory pain therapy...
  20. ncbi Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects
    Pierre Fontana
    Service d Hématologie Biologique A, Hôpital Européen Georges Pompidou and Inserm Unité 428, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Paris V, Paris, France
    Circulation 108:989-95. 2003
    ..Some studies have shown interindividual differences in ADP-induced platelet aggregation responses ex vivo, but the mechanisms underlying this variability are unknown...
  21. ncbi P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis
    Carlos Matute
    Departamento de Neurociencias, Universidad del Pais Vasco, 48940 Leioa, Spain
    J Neurosci 27:9525-33. 2007
    ..Thus, P2X(7) receptor antagonists may be beneficial for the treatment of MS...
  22. ncbi P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury
    Makoto Tsuda
    Division of Biosignaling, National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya, Tokyo 158 8501, Japan
    Nature 424:778-83. 2003
    ..Thus, blocking P2X4Rs in microglia might be a new therapeutic strategy for pain induced by nerve injury...
  23. pmc P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation
    Tuan Trang
    Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
    J Neurosci 29:3518-28. 2009
    ....
  24. pmc P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP
    Debra A Cockayne
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    J Physiol 567:621-39. 2005
    ..Taken together, these data extend our findings for P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder...
  25. ncbi Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production
    Rosalind A Le Feuvre
    School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
    J Biol Chem 277:3210-8. 2002
    ....
  26. ncbi A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor
    B J Gu
    Departments of Medicine and Anatomy and Histology, University of Sydney, Sydney, New South Wales 2006
    J Biol Chem 276:11135-42. 2001
    ..P2X(7)-mediated apoptosis of lymphocytes was impaired in homozygous mutant P2X(7) compared with germline (8.6 versus 35.2%). The data suggest that the glutamic acid at position 496 is required for optimal assembly of the P2X(7) receptor...
  27. ncbi P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease
    Lav K Parvathenani
    Neuroscience Drug Discovery, Pharmaceutical Research Institute, Bristol Myers Squibb Co, Wallingford, Connecticut 06492, USA
    J Biol Chem 278:13309-17. 2003
    ..Consistent with this hypothesis, P2X(7) receptor was specifically up-regulated around beta-amyloid plaques in a mouse model of Alzheimer's disease (Tg2576)...
  28. ncbi Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules
    Eduardo R Lazarowski
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365, Chapel Hill, NC 27599, USA
    Mol Pharmacol 64:785-95. 2003
  29. ncbi Functional and molecular diversity of purinergic ion channel receptors
    A B MacKenzie
    Institute of Molecular Physiology, University of Sheffield, England, UK
    Ann N Y Acad Sci 868:716-29. 1999
    ..Further phenotypes can be produced when two subunits are coexpressed, indicating hetero-multimerization. This chapter compares the properties of the native P2X receptors with those of the cloned and expressed subunits...
  30. pmc Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice
    C Leon
    Institut National de la Santé et de la Recherche Médicale INSERM U 311, Etablissement de Transfusion Sanguine, 10, rue Spielmann, B P 36, 67065 Strasbourg, France
    J Clin Invest 104:1731-7. 1999
    ..Hence, the P2Y(1) receptor plays an essential role in thrombotic states and represents a potential target for antithrombotic drugs...
  31. ncbi The P2X7 receptor: a key player in IL-1 processing and release
    Davide Ferrari
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Italy
    J Immunol 176:3877-83. 2006
    ....
  32. ncbi Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice
    J E Fabre
    Department of Medicine, University of North Carolina, CB 7248, Chapel Hill, Thurston Bowles Bld, Durham, North Carolina, USA
    Nat Med 5:1199-202. 1999
    ..These findings support the hypothesis that the ATP receptor P2Y1 is a principal receptor mediating both physiologic and pathological ADP-induced processes in platelets...
  33. ncbi Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. Phorbol ester or [Ca2+]i elevation can substitute for receptor activation
    S P Soltoff
    Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 273:23110-7. 1998
    ..Although P2Y2 and EGF receptors may both activate a similar multiprotein signaling cascade immediately upstream of MAP kinase, the P2Y2 receptor appears to uniquely utilize [Ca2+]i, PKC, and, subsequently, RAFTK...
  34. pmc Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells
    Eliana Scemes
    Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurosci 23:11444-52. 2003
    ....
  35. ncbi The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7)
    A Surprenant
    Glaxo Institute for Molecular Biology, Geneva, Switzerland
    Science 272:735-8. 1996
    ..Thus, the P2X7 (or P2Z) receptor is a bifunctional molecule that could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells...
  36. ncbi P2X7 receptors in the nervous system
    Beata Sperlagh
    Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H 1450 Budapest, Hungary
    Prog Neurobiol 78:327-46. 2006
    ....
  37. ncbi ATP-gated ion channel P2X(3) is increased in human inflammatory bowel disease
    Y Yiangou
    Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK
    Neurogastroenterol Motil 13:365-9. 2001
    ..01). In humans, unlike rodents, P2X(3) is thus not restricted to sensory neurones. Increased P2X(3) in inflamed intestine suggests a potential role in dysmotility and pain, for which it represents a new therapeutic target...
  38. ncbi Adenosine diphosphate (ADP)-induced thromboxane A(2) generation in human platelets requires coordinated signaling through integrin alpha(IIb)beta(3) and ADP receptors
    Jianguo Jin
    Department of Physiology, Temple University Medical School, Philadelphia, PA 19140, USA
    Blood 99:193-8. 2002
    ....
  39. ncbi Ticagrelor versus clopidogrel in patients with acute coronary syndromes
    Lars Wallentin
    Uppsala Clinical Research Center, Uppsala, Sweden
    N Engl J Med 361:1045-57. 2009
    ..Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel...
  40. ncbi The role of purinergic P2X7 receptors in the inflammation and fibrosis of unilateral ureteral obstruction in mice
    R G Gonçalves
    Lab Multidisciplinar de Pesquisa, Servico de Nefrologia, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
    Kidney Int 70:1599-606. 2006
    ..These findings constitute the first evidence that P2X7 receptors are implicated in macrophage infiltration, collagen deposition and apoptosis in response to ureteral obstruction in mice...
  41. pmc Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons
    Yong Chen
    Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 1069, USA
    Proc Natl Acad Sci U S A 105:16773-8. 2008
    ..Thus, direct blocking P2X7Rs, as proposed before, may not be the best strategy for reducing pain or lessening neuronal degeneration because it also disrupts the protective function of P2X7Rs...
  42. ncbi P2X(2)- and P2X(3)-positive fibers in fungiform papillae originate from the chorda tympani but not the trigeminal nerve in rats and mice
    Yusuke Ishida
    Department of Neurobiology and Anatomy, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467 8601, Japan
    J Comp Neurol 514:131-44. 2009
    ..Taken together, these findings suggest that most P2X(2) and P2X(3) receptors in fungiform papillae are used for gustation rather than somatosensation...
  43. pmc Analysis of assembly and trafficking of native P2X4 and P2X7 receptor complexes in rodent immune cells
    Miyyada Boumechache
    Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD
    J Biol Chem 284:13446-54. 2009
    ..2-fold increase in total expression. The redistribution of intracellular receptors is thus an efficient means of enhancing the functional expression of P2X4 at the plasma membrane of microglia...
  44. ncbi Amino acid residues involved in gating identified in the first membrane-spanning domain of the rat P2X(2) receptor
    L H Jiang
    Institute of Molecular Physiology, University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, United Kingdom
    J Biol Chem 276:14902-8. 2001
    ..The results suggest that Val(48) at the outer end of the first hydrophobic segment takes part in the gating movement of channel opening...
  45. ncbi Altered cytokine production in mice lacking P2X(7) receptors
    M Solle
    Department of Respiratory, Allergy, Immunology, Inflammation, and Infectious Diseases, Pfizer Inc, Groton, Connecticut 06340, USA
    J Biol Chem 276:125-32. 2001
    ..Together these results demonstrate that P2X(7)R activation can provide a signal that leads to maturation and release of IL-1 beta and initiation of a cytokine cascade...
  46. ncbi P2X7 receptor cell surface expression and cytolytic pore formation are regulated by a distal C-terminal region
    Megan L Smart
    Department of Physiology, The University of Melbourne, Victoria 3010, Australia
    J Biol Chem 278:8853-60. 2003
    ....
  47. ncbi Involvement of beta1 integrin in microglial chemotaxis and proliferation on fibronectin: different regulations by ADP through PKA
    Kaoru Nasu-Tada
    Division of Pharmacology, National Institute of Health Sciences, Setagaya, Tokyo, Japan
    Glia 52:98-107. 2005
    ..Together, these results indicate the involvement of beta1 integrin in microglial proliferation and chemotaxis, both of which have clinical importance. The data also suggest that PKA is inversely involved in these two cellular functions...
  48. ncbi An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor
    James S Wiley
    Department of Medicine, University of Sydney at Nepean Hospital, Penrith, New South Wales 2750, Australia
    J Biol Chem 278:17108-13. 2003
    ..These data identify a second loss-of-function polymorphism within the P2X(7) receptor and show that Ile-568 is critical to the trafficking domain, which we have shown to lie between residues 551 and 581...
  49. ncbi Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding
    Sebastien Roger
    Faculty of Life Science, University of Manchester, Manchester M13 9PT, United Kingdom
    J Neurosci 28:6393-401. 2008
    ..This is the first example of CaM deregulating, rather than tightly controlling, calcium entry through an ion channel...
  50. ncbi Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals
    L Vulchanova
    Graduate Program in Neuroscience, University of Minnesota, Minneapolis 55455, USA
    Neuropharmacology 36:1229-42. 1997
    ..These results suggest species differences, although a more extensive study of primate sensory systems is necessary...
  51. ncbi A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages
    Anne N Shemon
    Department of Medicine, University of Sydney, Level 5, Spurrett Building, Nepean Hospital, Penrith, New South Wales 2750, Australia
    J Biol Chem 281:2079-86. 2006
    ..Lymphocytes, monocytes, and macrophages from subjects homozygous for T357S or compound heterozygous for T357S and a second loss-of-function allele have reduced or absent P2X(7) receptor function...
  52. pmc Extracellular ATP causes ROCK I-dependent bleb formation in P2X7-transfected HEK293 cells
    Anna Morelli
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, and Interdisciplinary Center for the Study of Inflammation, University of Ferrara, I 44100 Ferrara, Italy
    Mol Biol Cell 14:2655-64. 2003
    ..These observations suggest that P2X7-dependent plasma membrane blebbing depends on the activation of the serine/threonine kinase ROCK I...
  53. pmc Regions of the amino terminus of the P2X receptor required for modification by phorbol ester and mGluR1alpha receptors
    Hairuo Wen
    Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK
    J Neurochem 108:331-40. 2009
    ..These results demonstrate that the conserved YXTXK/R sequence and a region with a conserved glycine residue close to the first transmembrane segment contribute to PMA and GPCR regulation of P2X(1) receptors...
  54. pmc P2X7 receptor-stimulated secretion of MHC class II-containing exosomes requires the ASC/NLRP3 inflammasome but is independent of caspase-1
    Yan Qu
    Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44120, USA
    J Immunol 182:5052-62. 2009
    ....
  55. ncbi N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors
    Lin Hua Jiang
    Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
    Am J Physiol Cell Physiol 289:C1295-302. 2005
    ..Together, the clear differential effects of extracellular sodium ions or of mutation of the receptor strongly suggest that N-methyl-d-glucamine and YO-PRO-1 do not enter the cell by the same permeation pathway...
  56. ncbi The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis
    S Jacquet
    INSERM U563, Dpt Lipoprotéines et Médiateurs Lipidiques, Bat C, Hopital Purpan, 31024 Toulouse, France
    Cell Mol Life Sci 62:2508-15. 2005
    ..We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y13-mediated HDL endocytosis...
  57. ncbi Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis
    Keiko Ohsawa
    Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo 187 8502, Japan
    Glia 55:604-16. 2007
    ..These results indicate that P2X(4)R as well as P2Y(12)R is involved in ATP-induced microglial chemotaxis...
  58. ncbi A loss-of-function polymorphism in the human P2X7 receptor abolishes ATP-mediated killing of mycobacteria
    Bernadette M Saunders
    Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW Australia
    J Immunol 171:5442-6. 2003
    ..These data demonstrate that a single nucleotide polymorphism in the P2X7 gene can allow survival of mycobacteria within infected host cells...
  59. ncbi Contribution of individual subunits to the multimeric P2X(2) receptor: estimates based on methanethiosulfonate block at T336C
    R Stoop
    Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Geneva, Switzerland
    Mol Pharmacol 56:973-81. 1999
    ..The present results show that a "per-subunit" channel block causes the blocking effects of MTSET and they suggest that not four but maximally three subunits actively participate in the channel formation...
  60. ncbi Regulation of immune response by P2X7 receptor
    Lanfen Chen
    Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave F 520, Bronx, NY 10461, USA
    Crit Rev Immunol 26:499-513. 2006
    ....
  61. ncbi The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis
    Nadia D'Ambrosi
    Santa Lucia Foundation, Rome, Italy
    J Immunol 183:4648-56. 2009
    ..Considering that extracellular ATP, through purinergic P2 receptors, constitutes a well recognized neuron-to-microglia alarm signal, the aim of this study was to investigate ..
  62. ncbi Adenosine triphosphate-induced shedding of CD23 and L-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases
    B Gu
    Sydney University Department of Medicine, Nepean Hospital, Penrith, Australia
    Blood 92:946-51. 1998
    ..However, different membrane metalloproteases seem to mediate the shedding of L-selectin and CD23...
  63. ncbi Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel
    J T Brandt
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Thromb Haemost 5:2429-36. 2007
    ..The pharmacodynamic response to clopidogrel is more variable than the response to prasugrel, but the reasons for variation in response to clopidogrel are not well characterized...
  64. ncbi Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen
    Mark P Kuehnel
    EMBL, Meyerhofstr 1, 69117 Heidelberg, Germany
    J Cell Sci 122:499-504. 2009
    ..In the accompanying paper by Kuehnel et al. (doi:10.1242/jcs.034207), more evidence is provided in support of this model from the analysis of actin assembly at the plasma membrane of intact macrophages...
  65. ncbi The P2X7 receptor as a therapeutic target
    Romeo Romagnoli
    Universita di Ferrara, Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara 17 19, 44100 Ferrara, Italy
    Expert Opin Ther Targets 12:647-61. 2008
    ....
  66. pmc Regulation of P2X2 receptors by the neuronal calcium sensor VILIP1
    Severine Chaumont
    Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Sci Signal 1:ra8. 2008
    ..Our data thus reveal a previously unrecognized function for the neuronal calcium sensor protein VILIP1 and a mechanism for regulation of ATP-dependent P2X receptor signaling by neuronal calcium sensors...
  67. ncbi Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor
    Sahil Adriouch
    Universite Denis Diderot, Paris, France
    J Immunol 169:4108-12. 2002
    ..The effects of the P451L mutation resemble those of the E496A mutation in human P2X(7)R. These P2X(7)R mutants may provide useful tools to decipher the molecular mechanisms leading to pore formation...
  68. ncbi Identification of a trafficking motif involved in the stabilization and polarization of P2X receptors
    Severine Chaumont
    Departement de Pharmacologie, Laboratoire de Génomique Fonctionnelle, CNRS UPR2580, 141 rue de la Cardonille, 34396 Montpellier, France
    J Biol Chem 279:29628-38. 2004
    ....
  69. pmc Disordered purinergic signaling inhibits pathological angiogenesis in cd39/Entpd1-null mice
    Shaun W Jackson
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Am J Pathol 171:1395-404. 2007
    ..Our data indicate novel links between CD39/ENTPD1, extracellular nucleotide-mediated signaling, and vascular endothelial cell integrin function that impact on angiogenesis and tumor growth...
  70. ncbi ATP signaling is crucial for communication from taste buds to gustatory nerves
    Thomas E Finger
    Rocky Mountain Taste and Smell Center, Aurora CO 80045, USA
    Science 310:1495-9. 2005
    ..Finally, stimulation of taste buds in vitro evokes release of ATP. Thus, ATP fulfils the criteria for a neurotransmitter linking taste buds to the nervous system...
  71. ncbi Exacerbation of experimental autoimmune encephalomyelitis in P2X7R-/- mice: evidence for loss of apoptotic activity in lymphocytes
    Lanfen Chen
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Immunol 176:3115-26. 2006
    ..From these data we conclude that enhanced susceptibility of P2X7R-/- mice to EAE reflects a loss of apoptotic activity in lymphocytes, supporting an important role for this receptor in lymphocyte homeostasis...
  72. ncbi Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes
    Robert F Storey
    Cardiovascular Research Unit, University of Sheffield, Sheffield, United Kingdom
    J Am Coll Cardiol 50:1852-6. 2007
    ..clopidogRel in non-ST-segment Elevation myocardial infarction)-2, we compared the antiplatelet effects of AZD6140 and clopidogrel and assessed the effects of AZD6140 in clopidogrel-pretreated patients...
  73. ncbi P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase
    W Panenka
    Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1
    J Neurosci 21:7135-42. 2001
    ..The regulation of MCP-1 in astrocytes by ATP may be important in mediating communication with hematopoietic inflammatory cells...
  74. ncbi Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus
    Beata Sperlagh
    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    J Neurochem 81:1196-211. 2002
    ..In conclusion, P2X7 Rs are localized to the excitatory terminals in the hippocampus, and their activation regulates the release of glutamate and GABA from themselves and from their target cells...
  75. pmc Activation and desensitization of the recombinant P2X1 receptor at nanomolar ATP concentrations
    Jürgen Rettinger
    Department of Molecular Pharmacology, Medical School, Technical University of Aachen, Germany
    J Gen Physiol 121:451-61. 2003
    ..Our results imply that nanomolar extracellular ATP concentrations can obscure P2X1 receptor responses by driving a significant fraction of the receptor pool into a long-lasting refractory closed state...
  76. ncbi Antinociceptive effect of a new P(2Z)/P2X7 antagonist, oxidized ATP, in arthritic rats
    Giacomo Dell'antonio
    Department of Pathology, IRCCS H S Raffaele, Via Olgettina 60, Milan, Italy
    Neurosci Lett 327:87-90. 2002
    ..The data indicate that the P2z/P2X7 receptor system exerts a role in nociception and that oATP, by inhibiting such a receptor, reduces the nociceptive signal in the course of peripheral inflammation...
  77. ncbi Upregulated expression of purinergic P2X(7) receptor in Alzheimer disease and amyloid-beta peptide-treated microglia and in peptide-injected rat hippocampus
    James G McLarnon
    Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver BC, Canada
    J Neuropathol Exp Neurol 65:1090-7. 2006
    ..The overall results suggest roles of P2X(7)R in mediating microglial purinergic inflammatory responses in AD brain...
  78. ncbi Desensitization, recovery and Ca(2+)-dependent modulation of ATP-gated P2X receptors in nociceptors
    S P Cook
    Vollum Institute L 474, Oregon Health Science University, Portland 97201 3098, USA
    Neuropharmacology 36:1303-8. 1997
    ..Mechanistic explanations for either the increase in transient current magnitude by elevated Ca2+ext, or persistent current overrecovery may reflect endogenous pathways for P2X receptor modulation...
  79. ncbi ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts: a novel role for the P2Y2 receptor in bone remodeling
    Astrid Hoebertz
    Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom
    J Cell Biochem 86:413-9. 2002
    ..These findings suggest that extracellular nucleotides could function locally as important negative modulators of bone metabolism, perhaps contributing to bone loss in a number of pathological states...
  80. pmc Interaction between cysteines introduced into each transmembrane domain of the rat P2X2 receptor
    Valeria Spelta
    Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
    Br J Pharmacol 138:131-6. 2003
    ..It reversed the rapid current deactivation at F44C/L338C. 5 The results suggest that a methanethiosulfonate binding to L338C prevents binding to F44C; this might indicate proximity of these two residues...
  81. pmc Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels
    Severine Chaumont
    Departments of Physiology and Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 105:12063-8. 2008
    ..Finally, the data illustrate the utility of a new approach, using tetracysteine tags and biarsenical fluorophores to measure site-specific conformational changes in membrane proteins...
  82. ncbi Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways
    Christelle D Douillet
    Division of Trauma and Critical Care, Department of Surgery, University of North Carolina at Chapel Hill, 4008 Burnett Womack, Chapel Hill, NC 27599 7228, USA
    Am J Physiol Lung Cell Mol Physiol 291:L734-46. 2006
    ..This effect is dependent on transcription and translation. Our findings were confirmed in an in vivo model, thus demonstrating a novel mechanism of nucleotide-induced IL-6 secretion by airway epithelia...
  83. pmc Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors
    Liaman K Mamedova
    Laboratory of Bioorganic Chemistry, Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, Bethesda, MD 20892 0810, USA
    Biochem Pharmacol 67:1763-70. 2004
    ..Thus, we have identified potent, insurmountable antagonists of P2Y(6) receptors that are selective within the family of PLC-coupled P2Y receptors...
  84. ncbi Cloning, pharmacological characterisation and distribution of the rat G-protein-coupled P2Y(13) receptor
    Marta Fumagalli
    Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy
    Biochem Pharmacol 68:113-24. 2004
    ....
  85. ncbi Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain
    Yo Sasaki
    Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan
    Glia 44:242-50. 2003
    ..Hardly any P2Y12 mRNA was detected in macrophages obtained from the spleen and abdominal cavity, which share many surface molecules with microglia...
  86. ncbi Selective nucleotide-release from dense-core granules in insulin-secreting cells
    Stefanie Obermuller
    Department of Experimental Medicinal Sciences, Lund University, BMC B11, SE 221 84 Lund, Sweden
    J Cell Sci 118:4271-82. 2005
    ..These observations suggest that insulin-secreting cells are able to use the same secretory vesicles to release small molecules either alone or together with the peptide hormone...
  87. ncbi Molecular characterization of the zebrafish P2X receptor subunit gene family
    S Kucenas
    Department of Pharmacological and Physiological Science, St Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA
    Neuroscience 121:935-45. 2003
    ..These results suggest that P2X receptors might play a role in the early development and/or function of the sensory nervous system in vertebrates...
  88. ncbi P2X7 nucleotide receptor activation enhances IFN gamma-induced type II nitric oxide synthase activity in BV-2 microglial cells
    Fernand Pierre Gendron
    Department of Biochemistry, University of Missouri Columbia, Columbia, Missouri 65212, USA
    J Neurochem 87:344-52. 2003
    ..These results suggest that activation of P2X7 receptors may contribute to inflammatory responses in microglial cells seen in neurodegenerative diseases...
  89. ncbi ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage
    V B Mehta
    Dorothy M. Davis Heart and Lung Research Institute and Pulmonary and Critical Care Division, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 276:3820-6. 2001
    ..Taken together, these results suggest that, although synthesis of IL-1beta and IL-18 differ, ATP-mediated release of both cytokines requires a priming step but not proteolytically functional caspase-1...
  90. ncbi P2 receptors activated by uracil nucleotides--an update
    Andreas Brunschweiger
    Pharmaceutical Institute, University of Bonn, Bonn, Germany
    Curr Med Chem 13:289-312. 2006
    ..They have also been proposed to play a role in neurodegenerative diseases. This article is an updated version of "P2-Pyrimidinergic Receptors and Their Ligands" by C. E. Müller published in Curr. Pharm. Des. 2002, 8, 2353-2369...
  91. pmc Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures
    Schuichi Koizumi
    Division of Pharmacology, National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya, Tokyo 158 8501, Japan
    Proc Natl Acad Sci U S A 100:11023-8. 2003
    ..We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via presynaptic mechanisms...
  92. ncbi Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP
    Giacomo Dell'antonio
    IRCCS Hospital San Raffaele, Milan, Italy
    Arthritis Rheum 46:3378-85. 2002
    ..This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws...
  93. ncbi P2X(7) receptors: properties and relevance to CNS function
    Shumin Duan
    Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Glia 54:738-46. 2006
    ....
  94. ncbi ATP stimulates mouse embryonic stem cell proliferation via protein kinase C, phosphatidylinositol 3-kinase/Akt, and mitogen-activated protein kinase signaling pathways
    Jung Sun Heo
    Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea
    Stem Cells 24:2637-48. 2006
    ..In conclusion, ATP stimulates mouse ESC proliferation through PKC, PI3K/Akt, and MAPKs via the P2 purinoceptors...
  95. ncbi P2X7 receptor polymorphism impairs extracellular adenosine 5'-triphosphate-induced interleukin-18 release from human monocytes
    R Sluyter
    Department of Medicine, University of Sydney at Nepean Hospital, Penrith NSW 2750, Australia
    Genes Immun 5:588-91. 2004
    ..ATP-induced ethidium(+) uptake in LPS-primed, monocytes of homozygous subjects was only 11% of that in wild-type monocytes, while P2X(7) surface expression on LPS-primed, homozygous monocytes was 44% of that on wild-type monocytes...
  96. ncbi An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor
    Ben J Gu
    Department of Medicine, University of Sydney at Nepean Hospital, Penrith, New South Wales 2750, Australia
    J Biol Chem 279:31287-95. 2004
    ....
  97. ncbi Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes
    B F King
    Autonomic Neuroscience Institute, Royal Free and University College Medical School, Royal Free Campus, Hampstead, London NW3 2PF, United Kingdom
    J Neurosci 20:4871-7. 2000
    ..Although homomeric P2X(6) receptors function poorly, the P2X(6) subunit can contribute to functional heteromeric P2X channels and may influence the phenotype of native P2X receptors in those cells in which it is expressed...
  98. pmc Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones
    I Shibuya
    Department of Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807 8555, Japan
    J Physiol 514:351-67. 1999
    ..Such ionic and Ca2+-signalling mechanisms triggered by ATP may play an important role in the regulation of SON neurosecretory cells...
  99. ncbi A 5' intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1-2% of the Caucasian population
    Kristen K Skarratt
    Department of Medicine, University of Sydney at Nepean Hospital, Penrith, NSW, Australia
    FEBS Lett 579:2675-8. 2005
    ..The splice site mutation is an inherited polymorphism and gives rise to a P2X(7) null allele in 1-2% of the Caucasian population...
  100. ncbi Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development
    C Agresti
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy
    Glia 50:132-44. 2005
    ..These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y(1) receptors...
  101. pmc Morphine enhances microglial migration through modulation of P2X4 receptor signaling
    Ryan J Horvath
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Neurosci 29:998-1005. 2009
    ..These data provide the first necessary step in supporting microglial migration as an attractive target for the prevention or attenuation of morphine-induced side effects including tolerance and hyperalgesia...

Research Grants62

  1. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
    ..An in-depth analysis of how CD-GEFI regulates platelet function in vitro and in vivo will aid in its establishment as a target for antiplatelet therapy. ..
  2. Novel Antithrombotic Diadenosine Tetraphosphate Analogs
    IVAN B YANACHKOV; Fiscal Year: 2010
    ..The new drug will complement related drugs under development for arterial thrombosis. ..
  3. Role of Beta 3 Integrin in Skeletal Metastasis
    Katherine Weilbaecher; Fiscal Year: 2009
    ..abstract_text> ..
  4. Regulation of Caspase-1 Signaling and Inflammation by the P2X7 ATP Receptor
    George R Dubyak; Fiscal Year: 2013
    ..These studies will provide mechanistic insights that may facilitate development of adjuvant purinergic receptor-based therapies which increase the efficacy of immunogenic anti-tumor responses to primary cancer chemotherapeutic agents. ..
  5. Coronary Physiology
    Eric O Feigl; Fiscal Year: 2010
    ..This is a resubmission of RO1 HL 082781-01-A1 (This time as a modular grant.) ..
  6. Targeting Adiponectin Signaling: Novel Peptide Therapy for Scleroderma
    John Varga; Fiscal Year: 2013
    ..The project is high impact since there are no approved treatments for scleroderma. Moreover, the results will have a strong impact on myriad fibrosing diseases that currently lack effective treatment. ..
  7. Antiplatelet Therapy: Platelet Inhibition, Polymorphisms, and Protein Biomarkers
    Marc S Sabatine; Fiscal Year: 2012
    ....
  8. STUDY OF ACTIVITY-DEPENDENT SYMPATHETIC SPROUTING
    Jun Ming Zhang; Fiscal Year: 2013
    ..We propose to continue the study of sympathetic component in neuropathic pain. Using a rat/mouse model, we will determine how abnormal activity, inflammation, ATP release affect sympathetic outgrowth and the neurons that sense pain. ..
  9. MOLECULAR BASIS FOR PLATELET FUNCTION IN HEMOSTASIS
    Robert Colman; Fiscal Year: 2004
    ..The knowledge gained from these studies will provide therapeutic approaches to enhancing hemostasis and preventing thrombosis. ..
  10. NPY AND ATP COTRANMISSION IN CHROMAFFIN CELLS
    TERRY HEXUM; Fiscal Year: 2003
    ..Information will be provided which may lead to improved therapy of diseases particularly involving aberrations in transmission by catecholamines e.g., epilepsy, anorexia, alcoholism, and hypertension. ..
  11. Enhancing Thrombostatin's Oral Delivery
    John Hilfinger; Fiscal Year: 2006
    ..This project specifically involves the development of a new oral drug to treat heart attacks and cancer. [unreadable] [unreadable] [unreadable]..
  12. PURINOCEPTOR CONTROL OF SURFACTANT SECRETION
    Ward Rice; Fiscal Year: 1991
    ....
  13. An ATP receptor-operated ionic conductance in Paramecium
    Todd Hennessey; Fiscal Year: 2002
    ....
  14. CONTROL OF LUNG SURFACTANT SECRETION IN THE NEWBORN
    SEAMUS ROONEY; Fiscal Year: 1999
    ..Such information is critical so that rational therapeutic interventions for prevention and/or control of the respiratory distress syndrome and other lung diseases may be developed. ..
  15. DEVELOPING SELECTIVE CALPAIN INHIBITORS
    ISAAC DONKOR; Fiscal Year: 2000
    ..The specific aims are: i) to identify the amino acid sequence at the active site of calpain to which inhibitors bind via affinity labeling; and ii) to synthesize compounds that will allow us to characterize the active site of calpain. ..
  16. ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW
    ERIC FEIGL; Fiscal Year: 2005
    ..The proposed basic research is fundamental to understanding the normal coronary physiology that underlies coronary artery disease. ..
  17. MECHANISM OF CATION TRANSPORT REGULATION
    Lewis Cantley; Fiscal Year: 1993
    ....
  18. INTERACTION OF PROGESTERONE RECEPTOR WITH ATP
    David Toft; Fiscal Year: 1980
    ..The studies of this proposal are designed to firmly establish the existence and properties of the ATP-Receptor interaction and to clearly identify and describe activities of the receptor that involve nucleotide interactions. ..
  19. MAMMALIAN SPERM SURFACE ORGANIZATION AND FUNCTION
    Diana Myles; Fiscal Year: 2002
    ..Furthermore, the identified, functional gamete proteins are potential targets for novel contraceptive methods based on pharmacological and immunological approaches. ..
  20. Prolonged and Severe Thrombocytopenia in Neonates
    Pamela Conley; Fiscal Year: 2006
    ..abstract_text> ..
  21. EPITHELIAL P2X PURINERGIC RECEPTOR CHANNELS
    Erik Schwiebert; Fiscal Year: 2003
    ..abstract_text> ..
  22. Nitric oxide in bladder neural-epithelial signaling
    Lori Birder; Fiscal Year: 2005
    ..Elucidation of mechanisms impacting on urothelial function may provide insights into the pathology of bladder dysfunction. ..
  23. Glial Signaling:Interplay of Connexins and P2 Receptors
    Eliana Scemes; Fiscal Year: 2006
    ....
  24. Regulation of Gliosis by Purinergic Receptor Signaling
    W Dalton Dietrich; Fiscal Year: 2006
    ..Thus, important advances in the understanding of the mechanisms underlying gliosis may provide new approaches to restore deficits in motor skills and cognitive functions caused by brain injury. [unreadable] [unreadable]..
  25. NTPDase2 expression and function in the liver
    JONATHAN DRANOFF; Fiscal Year: 2005
    ..The experiments proposed in these specific aims will provide the basis of several new lines of liver disease research and should provide novel therapeutic targets for treatment of cholestatic and fibrotic liver disease. ..
  26. EXTRACELLAR NUCLEOTIDE SIGNALING IN CYSTIC FIBROSIS
    Erik Schwiebert; Fiscal Year: 2004
    ..We are confident that novel results will be found concerning the cellular and molecular mechanisms of autocrine ATP release, signaling, and regulation of cell volume. ..
  27. Regulation of Bile Ductular Proliferation
    JONATHAN DRANOFF; Fiscal Year: 2009
    ..We anticipate that the results of these proposed experiments will lead to novel pharmacologic approaches for the regulation of bile ductular proliferation in biliary cirrhosis. ..
  28. Identification of a new protein that binds Src and PKC
    STEPHEN SOLTOFF; Fiscal Year: 2004
    ..Future efforts will determine if this new protein alters cell morphology, tight junction formation, or other functions in salivary cells. ..
  29. PARACRINE REGULATION OF BILE DUCT SECRETION BY ATP
    JONATHAN DRANOFF; Fiscal Year: 2004
    ..The Yale School of Medicine Department of Internal Medicine has pledged that the candidate will have extensive protected research time and excellent resources for the duration of the award. ..
  30. The function of RhoBTB proteins
    STEPHEN PAUL SOLTOFF; Fiscal Year: 2010
    ..The results of these studies may reveal a new pathway involved in the development of cancer and advance our understanding of the basic biology of transformation. ..
  31. HEART-LUNG PHYSIOLOGY: MOLECULAR-SYSTEMIC INTEGRATION
    William Schilling; Fiscal Year: 2008
    ..Our proposed training program, which emphasizes crossing of departmental barriers and scientific disciplines, continues to develop well-rounded scientists trained in integrated aspects of cardio-respiratory physiology. ..
  32. PRESYNAPTIC MECHANISMS IN THE INTESTINE
    James Galligan; Fiscal Year: 2008
    ..It is also anticipated that these studies will identify new targets for drugs that can be used to treat GI motility disorders. ..
  33. Characterization of cardiovascular purinoceptors
    TERRANCE EGAN; Fiscal Year: 2009
    ..This is important because the receptors may present a new and potentially exciting means of increasing the rate of survival of patients affected by a number of cardiovascular diseases including hypertension and heart failure. ..
  34. Functional G Protein pathways in platelet activation
    Satya P Kunapuli; Fiscal Year: 2010
    ..These studies will enhance our understanding of the signaling pathways and their role in platelet activation, and might identify potential newer targets for the treatment of thrombosis. ..
  35. Mechanisms of antibiotic action in Neisseria gonorrhoeae.
    Robert A Nicholas; Fiscal Year: 2010
    ..Together, these projects utilize genetic, biochemical, biophysical, and proteomics approaches to generate new insights into the mechanisms of antibiotic action in N. gonorrhoeae. ..
  36. PURINERGIC AXIS OF CARDIAC BLOOD VESSELS
    IAIN BUXTON; Fiscal Year: 2001
    ..We will approach these aims with biochemical, pharmacological, molecular, cell biological and microscopic methods employing intact blood vessels, cells in primary culture and subcellular fractions. ..
  37. Regulation of PMCA Pump-Channels by Oxidant Stress
    William P Schilling; Fiscal Year: 2010
    ..abstract_text> ..
  38. Trafficking/signaling of P2Y receptors in polarized epithelial cells
    Robert A Nicholas; Fiscal Year: 2011
    ..Our studies will provide novel and important information on the cellular mechanisms of P2Y receptor targeting and the regulation of P2Y receptor signaling activity in epithelial cells. ..
  39. Platelet ADP receptors
    Satya Kunapuli; Fiscal Year: 2008
    ..We further propose to evaluate the relative contribution of the P2Y1 and the P2Y12 receptors to thrombus formation, using P2Y1 or P2Y12 deficient mice and treatment with antagonists and models of in vivo thrombosis and thromboembolism. ..
  40. REGULATION OF PHOSPHOLIPASE C
    T Harden; Fiscal Year: 2002
    ..Completion of the work described in this proposal should considerably extend knowledge of the identify, specificity, and mechanism of interaction of the component proteins of the receptor-regulated inositol lipid signalling pathway. ..
  41. Genetic Predictors of Outcome in Acute MI
    Marc Sabatine; Fiscal Year: 2005
    ..Genomic control will be employed to detect and control for population stratification. Interaction terms will be incorporated into regression models to explore gene-environment and pharmacogenomic interactions. ..
  42. Vascular tone and blood pressure control during exercise
    John Buckwalter; Fiscal Year: 2005
    ..This is an issue of fundamental importance that may have important implications for individuals with peripheral vascular disease. ..
  43. Pediatric Interstitial Lung Disease Conference
    Robin Deterding; Fiscal Year: 2004
    ..Communication between clinical and basic scientists and an enhanced interest in PILD will certainly occur. Ultimately the care of children with these rare diseases will be improved and the field advanced. ..
  44. Role of Ion Channels in Cell Death
    William Schilling; Fiscal Year: 2005
    ..abstract_text> ..
  45. NUCLEOTIDE-MEDIATED LEUKOCYTE STIMULATION
    Satya Kunapuli; Fiscal Year: 2004
    ..The studies proposed in this application will also help us understand the mechanisms of neutrophil activation and contribute to the knowledge of better treatments and to the design of therapeutics for inflammatory diseases. ..
  46. P2T PURINERGIC RECEPTORS
    JOSE BOYER; Fiscal Year: 2004
    ..This information should prove useful in the development of new biochemical and pharmacological tools with potential use in the treatment of coagulation-related diseases. ..
  47. MOLECULAR BIOLOGY OF COLLAGEN RECEPTORS
    Thomas Kunicki; Fiscal Year: 2004
    ..The successful completion of the proposed studies will lead to a substantial increase in our understanding of the genetics and physiology of the platelet collagen receptor, GPVI. ..
  48. Ap4A as an Alarmone in Stress Physiology
    RICHARD HILDERMAN; Fiscal Year: 2003
    ..The information obtained in this proposal will give us insight on how to develop future proposals, biochemical and molecular experiments to determine the mechanism(s)by which Ap4A acts as an alarmone. ..
  49. Mechanisms of Nucleotide Release by Airway Epithelia
    Eduardo Lazarowski; Fiscal Year: 2006
    ..Delineation of nucleotide-releasing mechanisms will provide new possibilities to improve MCC function in chronic lung diseases characterized by mucin-obstructed and inflamed airways. [unreadable] [unreadable]..
  50. G protein signal integration by multifunctional proteins
    T Harden; Fiscal Year: 2006
    ..abstract_text> ..
  51. Ca2+ channels in non-excitable cells
    William Schilling; Fiscal Year: 2006
    ..abstract_text> ..
  52. Experimental approaches to understanding the ENS and its disorders
    James Galligan; Fiscal Year: 2006
    ..This will help the attendees develop a network of professional contacts who can help the young investigator in the career development process. [unreadable] [unreadable]..
  53. Gating and conduction of ATP-gated ion channels
    TERRANCE EGAN; Fiscal Year: 2007
    ..In the second set of experiments, fluorescence resonance energy transfer (FRET) will be used to determine intra- and inter-molecular distances in the absence and presence of ATP. ..
  54. Molecular Genetics of Integrin Collagen Receptors
    Thomas Kunicki; Fiscal Year: 2007
    ..From a clinical standpoint, these studies will also reveal the impact of these gene differences on risk for adverse events in bleeding disorders such as Von Willebrand Disease. ..
  55. CLEVELAND TRAINING PROGRAM IN CARDIOVASCULAR RESEARCH
    GEORGE DUBYAK; Fiscal Year: 2008
    ..The proposed renewal will continue to facilitate interaction among faculty and trainees and expand the culture and training excellence in cardiovascular research. ..
  56. CLASS B SCAVENGER RECEPTORS AND FOAM CELL FORMATION
    DENEYS VAN DER WESTHUYZEN; Fiscal Year: 2003
    ..The extent of atherosclerosis will be quantified by lesion size and cholesterol/cholesterol ester content. ..
  57. Alpha-Synuclein Conditional Knock-in Mice as Novel Models of Parkinson's Disease
    Darren Moore; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  58. Core Resources for Vision Research at MUSC
    Craig Crosson; Fiscal Year: 2007
    ..abstract_text> ..
  59. Adolescents at High Risk for Familial Bipolar Disorder
    John Nurnberger; Fiscal Year: 2009
    ..The ethical implications of this research will be studied by examining the effects of participation and the effect on self-esteem due to high- risk status. ..
  60. MULTI-PHOTON CONFOCAL MICROSCOPE SYSTEM
    Janos Peti Peterdi; Fiscal Year: 2008
    ..This multi-photon core is also critically needed for the USC Diabetes Research Center and the Clinical and Translational Science Institute, both being established pending PHS grants. [unreadable] [unreadable] [unreadable]..