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Cross-Talk in Nucleotide Signaling in Glioma C6 Cells

  • Dorota Wypych
  • Jolanta BarańskaEmail author
Chapter
  • 82 Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)

Abstract

The chapter is focused on the mechanism of action of metabotropic P2Y nucleotide receptors: P2Y1, P2Y2, P2Y12, P2Y14 and the ionotropic P2X7 receptor in glioma C6 cells. P2Y1 and P2Y12 both respond to ADP, but while P2Y1 links to PLC and elevates cytosolic Ca2+ concentration, P2Y12 negatively couples to adenylate cyclase, maintaining cAMP at low level. In glioma C6, these two P2Y receptors modulate activities of ERK1/2 and PI3K/Akt signaling and the effects depend on physiological conditions of the cells. During prolonged serum deprivation, cell growth is arrested, the expression of the P2Y1 receptor strongly decreases and P2Y12 becomes a major player responsible for ADP-evoked signal transduction. The P2Y12 receptor activates ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulates Akt activity, contributing to glioma invasiveness. In contrast, P2Y1 has an inhibitory effect on Akt pathway signaling. Furthermore, the P2X7 receptor, often responsible for apoptotic fate, is not involved in Ca2+elevation in C6 cells. The shift in nucleotide receptor expression from P2Y1 to P2Y12 during serum withdrawal, the cross talk between both receptors and the lack of P2X7 activity shows the precise self-regulating mechanism, enhancing survival and preserving the neoplastic features of C6 cells.

Keywords

P2Y1, P2Y2, P2Y12, P2Y14, P2X7 nucleotide receptors Serum withdrawal P2Y1/P2Y12 cross-talk cAMP ERK1/2 PI3K/Akt activity Glioma C6 cells 

Abbreviations

Akt

protein kinase B/Akt kinase

Ap4A

p1,p4-Di(adenosine-5′)tetraphosphate

BzATP

2’,3′- 0-(4-benzoylbenzoyl)-ATP

[Ca2+]i

intracellular calcium concentration

DAG

diacylglycerol

ER

endoplasmic reticulum

ERK1/2

extracellular signal-regulated kinases 1/2.

Gap1

GTP-ase activating protein 1

GBM

glioblastoma multiforme

GEF

guanine nucleotide exchange factor

GFAP

glial fibrillary acidic protein

GFP

green fluorescent protein

GPCRG

protein-coupled receptor

IP3

inositol-1,4,5-trisphosphate

LPS

lipopolysacharide

MEK

MAP kinase-ERK kinase

2MeSADP

2-methylthio ADP

OxATP

periodate-oxidized ATP

PDK1

phosphoinositide-dependent protein kinase 1.

PI3K

phosphatidylinositol 3-kinase

PIP2

phosphatidylinositol-4,5-bisphosphate

PKA

protein kinase A

PKC

protein kinase C

PLC

phospholipase C

PPADS

pyridoxal-phosphate-6-azophenyl-2,4disulfonic acid

PTEN

phosphatase and tensin homolog

PTX

pertussis toxin

RTK

receptor tyrosine kinase

References

  1. Abbracchio MP, Burnstock G (1994) Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther 64:445–475PubMedCrossRefGoogle Scholar
  2. Abbracchio MP, Verderio C (2006) Pathophysiological roles of P2 receptors in glial cells. Novartis Found Symp 276:91–103; discussion 103-112, 275-181PubMedPubMedCentralGoogle Scholar
  3. Abbracchio MP, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, King BF, Gachet C, Jacobson KA, Weisman GA, Burnstock G (2003) Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci 24:52–55.  https://doi.org/10.1016/S0165-6147(02)00038-X CrossRefPubMedGoogle Scholar
  4. Aerts I, Grobben B, Van Ostade X, Slegers H (2011) Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma. Eur J Pharmacol 654:1–9.  https://doi.org/10.1016/j.ejphar.2010.11.031 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Anderson CM, Nedergaard M (2006) Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trends Neurosci 29:257–262.  https://doi.org/10.1016/j.tins.2006.03.003 CrossRefPubMedGoogle Scholar
  6. Arslan G, Fredholm BB (2000) Stimulatory and inhibitory effects of adenosine a(2A) receptors on nerve growth factor-induced phosphorylation of extracellular regulated kinases 1/2 in PC12 cells. Neurosci Lett 292:183–186PubMedCrossRefPubMedCentralGoogle Scholar
  7. Auer RN, Del Maestro RF, Anderson R (1981) A simple and reproducible experimental in vivo glioma model. Can J Neurol Sci 8:325–331PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bagchi S, Liao Z, Gonzalez FA, Chorna NE, Seye CI, Weisman GA, Erb L (2005) The P2Y2 nucleotide receptor interacts with alphav integrins to activate go and induce cell migration. J Biol Chem 280:39050–39057.  https://doi.org/10.1074/jbc.M504819200 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Banachewicz W, Supłat D, Krzemiński P, Pomorski P, Barańska J (2005) P2 nucleotide receptors on C2C12 satellite cells. Purinergic Signal 1:249–257.  https://doi.org/10.1007/s11302-005-6311-0 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Barańska J, Chaban V, Czarny M, Sabała P (1995) Changes in Ca2+ concentration in phorbol ester and thapsigargin treated glioma C6 cells. The role of protein kinase C in regulation of Ca2+ entry. Cell Calcium 17:207–215PubMedCrossRefGoogle Scholar
  11. Barańska J, Czajkowski R, Sabała P (2004) Cross-talks between nucleotide receptor-induced signaling pathways in serum-deprived and non-starved glioma C6 cells. Adv Enzym Regul 44:219–232.  https://doi.org/10.1016/j.advenzreg.2003.11.001 CrossRefGoogle Scholar
  12. Barańska J, Czajkowski R, Pomorski P (2017) P2Y1 receptors – properties and functional activities. Adv Exp Med Biol – Protein Rev 19:71–89.  https://doi.org/10.1007/5584_2017_57 CrossRefGoogle Scholar
  13. Barth RF (1998) Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neuro-Oncol 36:91–102CrossRefGoogle Scholar
  14. Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370–371PubMedCrossRefGoogle Scholar
  15. Berridge MJ (1995) Capacitative calcium entry. Biochem J 312(Pt 1):1–11PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bezzi P, Volterra A (2001) A neuron-glia signalling network in the active brain. Curr Opin Neurobiol 11:387–394PubMedCrossRefGoogle Scholar
  17. Bianco F, Fumagalli M, Pravettoni E, D’Ambrosi N, Volonte C, Matteoli M, Abbracchio MP, Verderio C (2005) Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia. Brain Res Brain Res Rev 48:144–156.  https://doi.org/10.1016/j.brainresrev.2004.12.004 CrossRefPubMedGoogle Scholar
  18. Bianco F, Ceruti S, Colombo A, Fumagalli M, Ferrari D, Pizzirani C, Matteoli M, Di Virgilio F, Abbracchio MP, Verderio C (2006) A role for P2X7 in microglial proliferation. J Neurochem 99:745–758.  https://doi.org/10.1111/j.1471-4159.2006.04101.x CrossRefPubMedGoogle Scholar
  19. Bianco F, Colombo A, Saglietti L, Lecca D, Abbracchio MP, Matteoli M, Verderio C (2009) Different properties of P2X(7) receptor in hippocampal and cortical astrocytes. Purinergic Signal 5:233–240.  https://doi.org/10.1007/s11302-009-9137-3 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Boarder MR, Hourani SM (1998) The regulation of vascular function by P2 receptors: multiple sites and multiple receptors. Trends Pharmacol Sci 19:99–107PubMedCrossRefGoogle Scholar
  21. Boarder M, Webb TE (2001) P2Y receptors: structure and function. In: Abbracchio MP, Williams M (eds) Purinergic and pirimidinergic signalling. Springer, BerlinGoogle Scholar
  22. Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738.  https://doi.org/10.1038/nrm1197 CrossRefPubMedGoogle Scholar
  23. Boyer JL, Lazarowski ER, Chen XH, Harden TK (1993) Identification of a P2Y-purinergic receptor that inhibits adenylyl cyclase. J Pharmacol Exp Ther 267:1140–1146PubMedGoogle Scholar
  24. Braganhol E, Huppes D, Bernardi A, Wink MR, Lenz G, Battastini AM (2009) A comparative study of ectonucleotidase and P2 receptor mRNA profiles in C6 cell line cultures and C6 ex vivo glioma model. Cell Tissue Res 335:331–340.  https://doi.org/10.1007/s00441-008-0723-4 CrossRefPubMedGoogle Scholar
  25. Brazil DP, Hemmings BA (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26:657–664PubMedCrossRefGoogle Scholar
  26. Brismar T (1995) Physiology of transformed glial cells. Glia 15:231–243PubMedCrossRefGoogle Scholar
  27. Burnstock G (1997) The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36:1127–1139PubMedCrossRefGoogle Scholar
  28. Burnstock G (2002) Potential therapeutic targets in the rapidly expanding field of purinergic signalling. Clin Med 2:45–53CrossRefGoogle Scholar
  29. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797.  https://doi.org/10.1152/physrev.00043.2006 CrossRefPubMedGoogle Scholar
  30. Burnstock G (2015) Intracellular expression of purinoceptors. Purinergic Signal 11:275–276.  https://doi.org/10.1007/s11302-015-9455-6 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 96:4240–4245PubMedPubMedCentralCrossRefGoogle Scholar
  32. Carrasquero LM, Delicado EG, Jimenez AI, Perez-Sen R, Miras-Portugal MT (2005) Cerebellar astrocytes co-express several ADP receptors. Presence of functional P2Y(13)-like receptors. Purinergic Signal 1:153–159.  https://doi.org/10.1007/s11302-005-6211-3 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Carrasquero LM, Delicado EG, Bustillo D, Gutierrez-Martin Y, Artalejo AR, Miras-Portugal MT (2009) P2X7 and P2Y13 purinergic receptors mediate intracellular calcium responses to BzATP in rat cerebellar astrocytes. J Neurochem 110:879–889.  https://doi.org/10.1111/j.1471-4159.2009.06179.x CrossRefPubMedGoogle Scholar
  34. Carter RL, Fricks IP, Barrett MO, Burianek LE, Zhou Y, Ko H, Das A, Jacobson KA, Lazarowski ER, Harden TK (2009) Quantification of Gi-mediated inhibition of adenylyl cyclase activity reveals that UDP is a potent agonist of the human P2Y14 receptor. Mol Pharmacol 76:1341–1348.  https://doi.org/10.1124/mol.109.058578 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Chen L, Brosnan CF (2006) Regulation of immune response by P2X7 receptor. Crit Rev Immunol 26:499–513PubMedCrossRefGoogle Scholar
  36. Cheng X, Ji Z, Tsalkova T, Mei F (2008) Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin Shanghai 40:651–662PubMedPubMedCentralCrossRefGoogle Scholar
  37. Chiono M, Mahey R, Tate G, Cooper DM (1995) Capacitative Ca2+ entry exclusively inhibits cAMP synthesis in C6-2B glioma cells. Evidence that physiologically evoked Ca2+ entry regulates Ca(2+)-inhibitable adenylyl cyclase in non-excitable cells. J Biol Chem 270:1149–1155PubMedCrossRefGoogle Scholar
  38. Chou RC, Langan TJ (2003) In vitro synchronization of mammalian astrocytic cultures by serum deprivation. Brain Res Brain Res Protoc 11:162–167PubMedCrossRefGoogle Scholar
  39. Claes P, Grobben B, Van Kolen K, Roymans D, Slegers H (2001) P2Y(AC)(−)-receptor agonists enhance the proliferation of rat C6 glioma cells through activation of the p42/44 mitogen-activated protein kinase. Br J Pharmacol 134:402–408.  https://doi.org/10.1038/sj.bjp.0704271 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Claes P, Van Kolen K, Roymans D, Blero D, Vissenberg K, Erneux C, Verbelen JP, Esmans EL, Slegers H (2004) Reactive blue 2 inhibition of cyclic AMP-dependent differentiation of rat C6 glioma cells by purinergic receptor-independent inactivation of phosphatidylinositol 3-kinase. Biochem Pharmacol 67:1489–1498.  https://doi.org/10.1016/j.bcp.2003.12.017 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Collins VP (1998) Gliomas. Cancer Surv 32:37–51PubMedPubMedCentralGoogle Scholar
  42. Communi D, Govaerts C, Parmentier M, Boeynaems JM (1997) Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenylyl cyclase. J Biol Chem 272:31969–31973PubMedCrossRefPubMedCentralGoogle Scholar
  43. Communi D, Gonzalez NS, Detheux M, Brezillon S, Lannoy V, Parmentier M, Boeynaems JM (2001) Identification of a novel human ADP receptor coupled to G(i). J Biol Chem 276:41479–41485.  https://doi.org/10.1074/jbc.M105912200 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Czajkowski R, Barańska J (2002) Cross-talk between the ATP and ADP nucleotide receptor signalling pathways in glioma C6 cells. Acta Biochim Pol 49:877–889PubMedCrossRefPubMedCentralGoogle Scholar
  45. Czajkowski R, Lei L, Sabała P, Barańska J (2002) ADP-evoked phospholipase C stimulation and adenylyl cyclase inhibition in glioma C6 cells occur through two distinct nucleotide receptors, P2Y(1) and P2Y(12). FEBS Lett 513:179–183PubMedCrossRefPubMedCentralGoogle Scholar
  46. Czajkowski R, Banachewicz W, Ilnytska O, Drobot LB, Barańska J (2004) Differential effects of P2Y1 and P2Y12 nucleotide receptors on ERK1/ERK2 and phosphatidylinositol 3-kinase signalling and cell proliferation in serum-deprived and nonstarved glioma C6 cells. Br J Pharmacol 141:497–507.  https://doi.org/10.1038/sj.bjp.0705639 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Dahl D (1981) The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. J Neurosci Res 6:741–748.  https://doi.org/10.1002/jnr.490060608 CrossRefPubMedPubMedCentralGoogle Scholar
  48. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477.  https://doi.org/10.1038/24884 CrossRefPubMedPubMedCentralGoogle Scholar
  49. De Vuyst E, Decrock E, De Bock M, Yamasaki H, Naus CC, Evans WH, Leybaert L (2007) Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor. Mol Biol Cell 18:34–46.  https://doi.org/10.1091/mbc.e06-03-0182 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Di Virgilio F, Chiozzi P, Ferrari D, Falzoni S, Sanz JM, Morelli A, Torboli M, Bolognesi G, Baricordi OR (2001) Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97:587–600PubMedCrossRefPubMedCentralGoogle Scholar
  51. Di Virgilio F, Ben DD, Sarti AC, Giuliani AL, Falzoni S (2017) The P2X7 receptor in infection and inflamation. Immunity 47:15–31.  https://doi.org/10.1016/j.immuni.2017.06.0200 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Di Virgilio F, Guiliani AL, Vultagio-Poma V, Falzoni S, Alba CS (2018) Non-nucleotide agonists triggering P2X7 receptor activation and pore formation. Front Pharmacol 9:1–10.  https://doi.org/10.3389/fphar.2018.00039 CrossRefGoogle Scholar
  53. Duan S, Anderson CM, Keung EC, Chen Y, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23:1320–1328PubMedPubMedCentralCrossRefGoogle Scholar
  54. Dugan LL, Kim JS, Zhang Y, Bart RD, Sun Y, Holtzman DM, Gutmann DH (1999) Differential effects of cAMP in neurons and astrocytes. Role of B-raf. J Biol Chem 274:25842–25848PubMedCrossRefPubMedCentralGoogle Scholar
  55. Erb L, Weisman GA (2012) Coupling of P2Y receptors to G proteins and other signaling pathways. WIREs Membr Transport Signal 1:789–803.  https://doi.org/10.1002/wmts.62 CrossRefGoogle Scholar
  56. Erb L, Liu J, Ockerhausen J, Kong Q, Garrad RC, Griffin K, Neal C, Krugh B, Santiago-Perez LI, Gonzalez FA, Gresham HD, Turner JT, Weisman GA (2001) An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins and is required for G(o)-mediated signal transduction. J Cell Biol 153:491–501PubMedPubMedCentralCrossRefGoogle Scholar
  57. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Collo G, Buell G, Di Virgilio F (1997) ATP-mediated cytotoxicity in microglial cells. Neuropharmacology 36:1295–1301PubMedCrossRefPubMedCentralGoogle Scholar
  58. Fischer W, Appelt K, Grohmann M, Franke H, Norenberg W, Illes P (2009) Increase of intracellular Ca2+ by P2X and P2Y receptor-subtypes in cultured cortical astroglia of the rat. Neuroscience 160:767–783.  https://doi.org/10.1016/j.neuroscience.2009.02.026 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Fricks IP, Maddileti S, Carter RL, Lazarowski ER, Nicholas RA, Jacobson KA, Harden TK (2008) UDP is a competitive antagonist at the human P2Y14 receptor. J Pharmacol Exp Ther 325:588–594.  https://doi.org/10.1124/jpet.108.136309 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Fricks IP, Carter RL, Lazarowski ER, Harden TK (2009) Gi-dependent cell signaling responses of the human P2Y14 receptor in model cell systems. J Pharmacol Exp Ther 330:162–168.  https://doi.org/10.1124/jpet.109.150730 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Fumagalli M, Brambilla R, D’Ambrosi N, Volonte C, Mateoli M, Verderio C, Abbracchio MP (2003) Nucleotide-mediated calcium signaling in rat cortical astrocytes: role of P2X and P2Y receptors. Glia 43:218–230PubMedCrossRefGoogle Scholar
  62. Fumagalli M, Trincavelli L, Lecca D, Martini C, Ciana P, Abbracchio MP (2004) Cloning, pharmacological characterisation and distribution of the rat G-protein-coupled P2Y(13) receptor. Biochem Pharmacol 68:113–124.  https://doi.org/10.1016/j.bcp.2004.02.038 CrossRefPubMedGoogle Scholar
  63. Furnari FB, Huang HJ, Cavenee WK (1998) The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 58:5002–5008PubMedGoogle Scholar
  64. Gachet C (2006) Regulation of platelet functions by P2 receptors. Annu Rev Pharmacol Toxicol 46:277–300.  https://doi.org/10.1146/annurev.pharmtox.46.120604.141207 CrossRefPubMedGoogle Scholar
  65. Grobben B, Claes P, Van Kolen K, Roymans D, Fransen P, Sys SU, Slegers H (2001) Agonists of the P2Y(AC)-receptor activate MAP kinase by a ras-independent pathway in rat C6 glioma. J Neurochem 78:1325–1338PubMedCrossRefGoogle Scholar
  66. Grobben B, De Deyn PP, Slegers H (2002) Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res 310:257–270.  https://doi.org/10.1007/s00441-002-0651-7 CrossRefPubMedGoogle Scholar
  67. Guo LH, Trautmann K, Schluesener HJ (2004) Expression of P2X4 receptor in rat C6 glioma by tumor-associated macrophages and activated microglia. J Neuroimmunol 152:67–72.  https://doi.org/10.1016/j.jneuroim.2004.04.005 CrossRefPubMedGoogle Scholar
  68. Hanson MG Jr, Shen S, Wiemelt AP, McMorris FA, Barres BA (1998) Cyclic AMP elevation is sufficient to promote the survival of spinal motor neurons in vitro. J Neurosci 18:7361–7371PubMedPubMedCentralCrossRefGoogle Scholar
  69. Harden K, Barnard EA, Boeynaems JM, Burnstock G, Dubyak G, Hourani SM, Insel PA (1998) P2Y receptors. In: Girdlestone D (ed) The IUPHAR compendium of receptor characterization and classification, 2nd edn. IUPHAR Media Ltd, LondonGoogle Scholar
  70. Harden TK, Sesma JI, Fricks IP, Lazarowski ER (2010) Signalling and pharmacological properties of the P2Y14 receptor. Acta Physiol (Oxf) 199:149–160.  https://doi.org/10.1111/j.1748-1716.2010.02116.x CrossRefGoogle Scholar
  71. Hirano Y, Okajima F, Tomura H, Majid MA, Takeuchi T, Kondo Y (1991) Change of intracellular calcium of neural cells induced by extracellular ATP. FEBS Lett 284:235–237PubMedCrossRefGoogle Scholar
  72. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (2001) Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409:202–207.  https://doi.org/10.1038/35051599 CrossRefPubMedGoogle Scholar
  73. Illes P, Alexandre Ribeiro J (2004) Molecular physiology of P2 receptors in the central nervous system. Eur J Pharmacol 483:5–17PubMedCrossRefGoogle Scholar
  74. Ito A, Satoh T, Kaziro Y, Itoh H (1995) G protein beta gamma subunit activates Ras, Raf, and MAP kinase in HEK 293 cells. FEBS Lett 368:183–187PubMedCrossRefGoogle Scholar
  75. Jalink K, Hordijk PL, Moolenaar WH (1994) Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator. Biochim Biophys Acta 1198:185–196PubMedGoogle Scholar
  76. Jin J, Tomlinson W, Kirk IP, Kim YB, Humphries RG, Kunapuli SP (2001) The C6-2B glioma cell P2Y(AC) receptor is pharmacologically and molecularly identical to the platelet P2Y(12) receptor. Br J Pharmacol 133:521–528.  https://doi.org/10.1038/sj.bjp.0704114 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Kim S, Jee K, Kim D, Koh H, Chung J (2001) Cyclic AMP inhibits Akt activity by blocking the membrane localization of PDK1. J Biol Chem 276:12864–12870.  https://doi.org/10.1074/jbc.M001492200 CrossRefPubMedGoogle Scholar
  78. Kim SG, Gao ZG, Soltysiak KA, Chang TS, Brodie C, Jacobson KA (2003) P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis. Cell Mol Neurobiol 23:401–418PubMedPubMedCentralCrossRefGoogle Scholar
  79. King BF, Burnstock G, Boyer JL, Boeynaems J-M, Weisman GA, Kennedy C, Jacobson KA, Humphries RG, Abbracchio MP, Miras-Portugal MT (2000) The P2Y receptors. In: Girdlestone D (ed) The IUPHAR compendium of receptor characterization and classification, 2nd edn. IUPHAR Media Ltd., LondonGoogle Scholar
  80. Kitanaka J, Hashimoto H, Gotoh M, Mayumi T, Baba A (1992) Mechanism of extracellular ATP-stimulated phosphoinositide hydrolysis in rat glioma C6 cells. J Pharmacol Exp Ther 263:1248–1252PubMedGoogle Scholar
  81. Kopperud R, Krakstad C, Selheim F, Doskeland SO (2003) cAMP effector mechanisms. Novel twists for an ‘old’ signaling system. FEBS Lett 546:121–126PubMedCrossRefGoogle Scholar
  82. Koschel K, Tas PW (1993) Lysophosphatidic acid reverts the beta-adrenergic agonist-induced morphological response in C6 rat glioma cells. Exp Cell Res 206:162–166PubMedCrossRefGoogle Scholar
  83. Kranenburg O, Moolenaar WH (2001) Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists. Oncogene 20:1540–1546.  https://doi.org/10.1038/sj.onc.1204187 CrossRefPubMedGoogle Scholar
  84. Krzemiński P, Supłat D, Czajkowski R, Pomorski P, Barańska J (2007) Expression and functional characterization of P2Y1 and P2Y12 nucleotide receptors in long-term serum-deprived glioma C6 cells. FEBS J 274:1970–1982.  https://doi.org/10.1111/j.1742-4658.2007.05741.x CrossRefPubMedGoogle Scholar
  85. Krzemiński P, Pomorski P, Barańska J (2008) The P2Y14 receptor activity in glioma C6 cells. Eur J Pharmacol 594:49–54.  https://doi.org/10.1016/j.ejphar.2008.06.092 CrossRefPubMedGoogle Scholar
  86. Kubiatowski T, Jang T, Lachyankar MB, Salmonsen R, Nabi RR, Quesenberry PJ, Litofsky NS, Ross AH, Recht LD (2001) Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J Neurosurg 95:480–488.  https://doi.org/10.3171/jns.2001.95.3.0480 CrossRefPubMedGoogle Scholar
  87. Kurino M, Fukunaga K, Ushio Y, Miyamoto E (1996) Cyclic AMP inhibits activation of mitogen-activated protein kinase and cell proliferation in response to growth factors in cultured rat cortical astrocytes. J Neurochem 67:2246–2255PubMedCrossRefGoogle Scholar
  88. Lazarowski E (2006) Regulated release of nucleotides and UDP sugars from astrocytoma cells. Novartis Found Symp 276:73–84; discussion 84-90, 107-112, 275-181PubMedGoogle Scholar
  89. Leon C, Hechler B, Vial C, Leray C, Cazenave JP, Gachet C (1997) The P2Y1 receptor is an ADP receptor antagonized by ATP and expressed in platelets and megakaryoblastic cells. FEBS Lett 403:26–30PubMedCrossRefGoogle Scholar
  90. Liao Z, Seye CI, Weisman GA, Erb L (2007) The P2Y2 nucleotide receptor requires interaction with alpha v integrins to access and activate G12. J Cell Sci 120:1654–1662.  https://doi.org/10.1242/jcs.03441 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Lin WW, Chuang DM (1993) Extracellular ATP stimulates inositol phospholipid turnover and calcium influx in C6 glioma cells. Neurochem Res 18:681–687PubMedCrossRefGoogle Scholar
  92. Lin WW, Chuang DM (1994) Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma cells. J Pharmacol Exp Ther 269:926–931PubMedGoogle Scholar
  93. Locovei S, Scemes E, Qiu F, Spray DC, Dahl G (2007) Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett 581:483–488.  https://doi.org/10.1016/j.febslet.2006.12.056 CrossRefPubMedPubMedCentralGoogle Scholar
  94. McKenzie FR, Pouyssegur J (1996) cAMP-mediated growth inhibition in fibroblasts is not mediated via mitogen-activated protein (MAP) kinase (ERK) inhibition. cAMP-dependent protein kinase induces a temporal shift in growth factor-stimulated MAP kinases. J Biol Chem 271:13476–13483PubMedCrossRefGoogle Scholar
  95. Messens J, Slegers H (1992) Synthesis of glial fibrillary acidic protein in rat C6 glioma in chemically defined medium: cyclic AMP-dependent transcriptional and translational regulation. J Neurochem 58:2071–2080PubMedCrossRefGoogle Scholar
  96. Moolenaar WH (1999) Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res 253:230–238.  https://doi.org/10.1006/excr.1999.4702 CrossRefPubMedGoogle Scholar
  97. Moore DJ, Murdock PR, Watson JM, Faull RL, Waldvogel HJ, Szekeres PG, Wilson S, Freeman KB, Emson PC (2003) GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function. Brain Res Mol Brain Res 118:10–23PubMedCrossRefGoogle Scholar
  98. Neary JT, Zimmermann H (2009) Trophic functions of nucleotides in the central nervous system. Trends Neurosci 32:189–198.  https://doi.org/10.1016/j.tins.2009.01.002 CrossRefPubMedGoogle Scholar
  99. Nicholas RA, Watt WC, Lazarowski ER, Li Q, Harden K (1996) Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor. Mol Pharmacol 50:224–229PubMedGoogle Scholar
  100. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067.  https://doi.org/10.1152/physrev.00015.2002 CrossRefPubMedGoogle Scholar
  101. North RA, Surprenant A (2000) Pharmacology of cloned P2X receptors. Annu Rev Pharmacol Toxicol 40:563–580.  https://doi.org/10.1146/annurev.pharmtox.40.1.563 CrossRefPubMedGoogle Scholar
  102. Oey J (1975) Noradrealine induces morphological alterations in nucleated and enucleated rat C6 glioma cells. Nature 257:317–319PubMedCrossRefGoogle Scholar
  103. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082.  https://doi.org/10.1038/sj.emboj.7601378 CrossRefPubMedPubMedCentralGoogle Scholar
  104. Putney JW Jr, Bird GS (1993) The inositol phosphate-calcium signaling system in nonexcitable cells. Endocr Rev 14:610–631.  https://doi.org/10.1210/edrv-14-5-610 CrossRefPubMedGoogle Scholar
  105. Qiu W, Zhuang S, von Lintig FC, Boss GR, Pilz RB (2000) Cell type-specific regulation of B-Raf kinase by cAMP and 14-3-3 proteins. J Biol Chem 275:31921–31929.  https://doi.org/10.1074/jbc.M003327200 CrossRefPubMedGoogle Scholar
  106. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492PubMedGoogle Scholar
  107. Roymans D, Grobben B, Claes P, Slegers H (2001) Protein tyrosine kinase-dependent regulation of adenylate cyclase and phosphatidylinositol 3-kinase activates the expression of glial fibrillary acidic protein upon induction of differentiation in rat c6 glioma. Cell Biol Int 25:467–474.  https://doi.org/10.1006/cbir.2000.0636 CrossRefPubMedGoogle Scholar
  108. Ryten M, Dunn PM, Neary JT, Burnstock G (2002) ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells. J Cell Biol 158:345–355.  https://doi.org/10.1083/jcb.200202025 CrossRefPubMedPubMedCentralGoogle Scholar
  109. Ryu JK, Jantaratnotai N, Serrano-Perez MC, McGeer PL, McLarnon JG (2011) Block of purinergic P2X7R inhibits tumor growth in a C6 glioma brain tumor animal model. J Neuropathol Exp Neurol 70:13–22.  https://doi.org/10.1097/NEN.0b013e318201d4d4 CrossRefPubMedGoogle Scholar
  110. Sabała P, Czajkowski R, Przybyłek K, Kalita K, Kaczmarek L, Barańska J (2001) Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells. Br J Pharmacol 132:393–402.  https://doi.org/10.1038/sj.bjp.0703843 CrossRefPubMedPubMedCentralGoogle Scholar
  111. Sak K, Illes P (2005) Neuronal and glial cell lines as model systems for studying P2Y receptor pharmacology. Neurochem Int 47:401–412.  https://doi.org/10.1016/j.neuint.2005.05.012 CrossRefPubMedGoogle Scholar
  112. Salcman M (1995) Glioblastoma and malignant astrocytoma. In: Kaye AH, Laws ER (eds) Brain tumors: an encyclopedic approach. Churchill Livingstone, New YorkGoogle Scholar
  113. Savi P, Labouret C, Delesque N, Guette F, Lupker J, Herbert JM (2001) P2y(12), a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun 283:379–383.  https://doi.org/10.1006/bbrc.2001.4816 CrossRefPubMedGoogle Scholar
  114. Schachter JB, Li Q, Boyer JL, Nicholas RA, Harden TK (1996) Second messenger cascade specificity and pharmacological selectivity of the human P2Y1-purinoceptor. Br J Pharmacol 118:167–173PubMedPubMedCentralCrossRefGoogle Scholar
  115. Schachter JB, Boyer JL, Li Q, Nicholas RA, Harden TK (1997) Fidelity in functional coupling of the rat P2Y1 receptor to phospholipase C. Br J Pharmacol 122:1021–1024.  https://doi.org/10.1038/sj.bjp.0701479 CrossRefPubMedPubMedCentralGoogle Scholar
  116. Scrivens M, Dickenson JM (2005) Functional expression of the P2Y14 receptor in murine T-lymphocytes. Br J Pharmacol 146:435–444.  https://doi.org/10.1038/sj.bjp.0706322 CrossRefPubMedPubMedCentralGoogle Scholar
  117. Scrivens M, Dickenson JM (2006) Functional expression of the P2Y14 receptor in human neutrophils. Eur J Pharmacol 543:166–173.  https://doi.org/10.1016/j.ejphar.2006.05.037 CrossRefPubMedPubMedCentralGoogle Scholar
  118. Skelton L, Cooper M, Murphy M, Platt A (2003) Human immature monocyte-derived dendritic cells express the G protein-coupled receptor GPR105 (KIAA0001, P2Y14) and increase intracellular calcium in response to its agonist, uridine diphosphoglucose. J Immunol 171:1941–1949PubMedCrossRefGoogle Scholar
  119. Sliwa M, Markovic D, Gabrusiewicz K, Synowitz M, Glass R, Zawadzka M, Wesolowska A, Kettenmann H, Kaminska B (2007) The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin a. Brain 130:476–489.  https://doi.org/10.1093/brain/awl263 CrossRefPubMedGoogle Scholar
  120. Sluyter R (2017) The P2X7 receptor. Adv Exp Med Biol – Protein Rev 19:17–53.  https://doi.org/10.1007/5584_2017_59 CrossRefGoogle Scholar
  121. Soulet C, Sauzeau V, Plantavid M, Herbert JM, Pacaud P, Payrastre B, Savi P (2004) Gi-dependent and -independent mechanisms downstream of the P2Y12 ADP-receptor. J Thromb Haemost 2:135–146PubMedCrossRefGoogle Scholar
  122. Soulet C, Hechler B, Gratacap MP, Plantavid M, Offermanns S, Gachet C, Payrastre B (2005) A differential role of the platelet ADP receptor P2Y1 and P2Y12 in Rac activation. J Thromb Haemost 3:2296–2306.  https://doi.org/10.1111/j.1538-7836.2005.01588.x CrossRefPubMedGoogle Scholar
  123. Srinivas M, Calderon DP, Kronengold J, Verselis VK (2006) Regulation of connexin hemichannels by monovalent cations. J Gen Physiol 127:67–75.  https://doi.org/10.1085/jgp.200509397 CrossRefPubMedPubMedCentralGoogle Scholar
  124. Stork PJ, Schmitt JM (2002) Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation. Trends Cell Biol 12:258–266PubMedCrossRefGoogle Scholar
  125. Supłat-Wypych D, Dygas A, Barańska J (2010) 2′, 3′-O-(4-benzoylbenzoyl)-ATP-mediated calcium signaling in rat glioma C6 cells: role of the P2Y(2) nucleotide receptor. Purinergic Signal 6:317–325.  https://doi.org/10.1007/s11302-010-9194-7 CrossRefPubMedPubMedCentralGoogle Scholar
  126. Sutherland EW (1972) Studies on the mechanism of hormone action. Science 177:401–408PubMedCrossRefGoogle Scholar
  127. Tas PW, Koschel K (1998) Sphingosine-1-phosphate induces a Ca2+ signal in primary rat astrocytes and a Ca2+ signal and shape changes in C6 rat glioma cells. J Neurosci Res 52:427–434.  https://doi.org/10.1002/(SICI)1097-4547(19980515)52:4<427::AID-JNR6>3.0.CO;2-B CrossRefPubMedGoogle Scholar
  128. Tu MT, Luo SF, Wang CC, Chien CS, Chiu CT, Lin CC, Yang CM (2000) P2Y(2) receptor-mediated proliferation of C(6) glioma cells via activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 129:1481–1489.  https://doi.org/10.1038/sj.bjp.0703182 CrossRefPubMedPubMedCentralGoogle Scholar
  129. van Corven EJ, Groenink A, Jalink K, Eichholtz T, Moolenaar WH (1989) Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell 59:45–54PubMedCrossRefGoogle Scholar
  130. Van Kolen K, Slegers H (2004) P2Y12 receptor stimulation inhibits beta-adrenergic receptor-induced differentiation by reversing the cyclic AMP-dependent inhibition of protein kinase B. J Neurochem 89:442–453.  https://doi.org/10.1111/j.1471-4159.2004.02339.x CrossRefPubMedPubMedCentralGoogle Scholar
  131. Van Kolen K, Slegers H (2006a) Atypical PKCzeta is involved in RhoA-dependent mitogenic signaling by the P2Y(12) receptor in C6 cells. FEBS J 273:1843–1854.  https://doi.org/10.1111/j.1742-4658.2006.05205.x CrossRefPubMedGoogle Scholar
  132. Van Kolen K, Slegers H (2006b) Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks. Purinergic Signal 2:451–469.  https://doi.org/10.1007/s11302-006-9008-0 CrossRefPubMedPubMedCentralGoogle Scholar
  133. van Koppen C, Meyer zu Heringdorf D, Laser KT, Zhang C, Jakobs KH, Bunemann M, Pott L (1996) Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine-1-phosphate. J Biol Chem 271:2082–2087PubMedCrossRefPubMedCentralGoogle Scholar
  134. Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ (1997) cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 89:73–82PubMedCrossRefPubMedCentralGoogle Scholar
  135. Wan G, Zhou L, Lim QE, Wong YH, Too HP (2011) Cyclic AMP signalling through PKA but not Epac is essential for neurturin-induced biphasic ERK1/2 activation and neurite outgrowths through GFRalpha2 isoforms. Cell Signal 23:1727–1737.  https://doi.org/10.1016/j.cellsig.2011.06.007 CrossRefPubMedPubMedCentralGoogle Scholar
  136. Wang L, Liu F, Adamo ML (2001) Cyclic AMP inhibits extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways by inhibiting Rap1. J Biol Chem 276:37242–37249.  https://doi.org/10.1074/jbc.M105089200 CrossRefPubMedPubMedCentralGoogle Scholar
  137. Wang M, Kong Q, Gonzalez FA, Sun G, Erb L, Seye C, Weisman GA (2005) P2Y nucleotide receptor interaction with alpha integrin mediates astrocyte migration. J Neurochem 95:630–640.  https://doi.org/10.1111/j.1471-4159.2005.03408.x CrossRefPubMedPubMedCentralGoogle Scholar
  138. Webb TE, Feolde E, Vigne P, Neary JT, Runberg A, Frelin C, Barnard EA (1996) The P2Y purinoceptor in rat brain microvascular endothelial cells couple to inhibition of adenylate cyclase. Br J Pharmacol 119:1385–1392PubMedPubMedCentralCrossRefGoogle Scholar
  139. Weber G (2002) Reciprocal regulation: recognition of pattern of gene expression in cancer cells. Adv Enzym Regul 42:83–100CrossRefGoogle Scholar
  140. Wei W, Ryu JK, Choi HB, McLarnon JG (2008) Expression and function of the P2X(7) receptor in rat C6 glioma cells. Cancer Lett 260:79–87.  https://doi.org/10.1016/j.canlet.2007.10.025 CrossRefPubMedGoogle Scholar
  141. White N, Burnstock G (2006) P2 receptors and cancer. Trends Pharmacol Sci 27:211–217.  https://doi.org/10.1016/j.tips.2006.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  142. Wildman SS, Unwin RJ, King BF (2003) Extended pharmacological profiles of rat P2Y2 and rat P2Y4 receptors and their sensitivity to extracellular H+ and Zn2+ ions. Br J Pharmacol 140:1177–1186.  https://doi.org/10.1038/sj.bjp.0705544 CrossRefPubMedPubMedCentralGoogle Scholar
  143. Wypych D, Pomorski P (2012) P2Y1 nucleotide receptor silencing and its effect on glioma C6 calcium signaling. Acta Biochim Pol 59:711–717.  https://doi.org/10.18388/abp.2012_2115 CrossRefPubMedGoogle Scholar
  144. Zhang FL, Luo L, Gustafson E, Palmer K, Qiao X, Fan X, Yang S, Laz TM, Bayne M, Monsma F Jr (2002) P2Y(13): identification and characterization of a novel Galphai-coupled ADP receptor from human and mouse. J Pharmacol Exp Ther 301:705–713PubMedCrossRefGoogle Scholar
  145. Zimmermann H (2000) Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedeberg’s Arch Pharmacol 362:299–309CrossRefGoogle Scholar
  146. Zwartkruis FJ, Bos JL (1999) Ras and Rap1: two highly related small GTPases with distinct function. Exp Cell Res 253:157–165.  https://doi.org/10.1006/excr.1999.4695 CrossRefPubMedGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Nencki Institute of Experimental BiologyPolish Academy of SciencesWarsawPoland

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