Cellular and Molecular Life Sciences

, Volume 68, Issue 8, pp 1369–1394 | Cite as

Purinergic signaling in embryonic and stem cell development



Nucleotides are of crucial importance as carriers of energy in all organisms. However, the concept that in addition to their intracellular roles, nucleotides act as extracellular ligands specifically on receptors of the plasma membrane took longer to be accepted. Purinergic signaling exerted by purines and pyrimidines, principally ATP and adenosine, occurs throughout embryologic development in a wide variety of organisms, including amphibians, birds, and mammals. Cellular signaling, mediated by ATP, is present in development at very early stages, e.g., gastrulation of Xenopus and germ layer definition of chick embryo cells. Purinergic receptor expression and functions have been studied in the development of many organs, including the heart, eye, skeletal muscle and the nervous system. In vitro studies with stem cells revealed that purinergic receptors are involved in the processes of proliferation, differentiation, and phenotype determination of differentiated cells. Thus, nucleotides are able to induce various intracellular signaling pathways via crosstalk with other bioactive molecules acting on growth factor and neurotransmitter receptors. Since normal development is disturbed by dysfunction of purinergic signaling in animal models, further studies are needed to elucidate the functions of purinoceptor subtypes in developmental processes.


ATP Cell death CNS Differentiation Heart Muscle Proliferation 


  1. 1.
    Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797PubMedGoogle Scholar
  2. 2.
    Kupitz Y, Atlas D (1993) A putative ATP-activated Na + channel involved in sperm-induced fertilization. Science 261:484–486PubMedGoogle Scholar
  3. 3.
    Smith R, Koenig C, Pereda J (1983) Adenosinetriphosphatase (Mg-ATPase) activity in the plasma membrane of preimplantation mouse embryo as revealed by electron microscopy. Anat Embryol (Berl) 168:455–466Google Scholar
  4. 4.
    Ishikawa T, Seguchi H (1985) Localization of Mg++-dependent adenosine triphosphatase and alkaline phosphatase activities in the postimplantation mouse embryos in day 5 and 6. Anat Embryol (Berl) 173:7–11Google Scholar
  5. 5.
    Foresta C, Rossato M, Di Virgilio F (1992) Extracellular ATP is a trigger for the acrosome reaction in human spermatozoa. J Biol Chem 267:1–5Google Scholar
  6. 6.
    Burnstock G (2001) Purinergic signalling in development. In: Abbracchio MP, Williams M (eds) Handbook of experimental pharmacology, vol 151/I. Purinergic and pyrimidinergic signalling I: molecular nervous and urinogenitary system function. Springer, Berlin Heidelberg New York, pp 89–127Google Scholar
  7. 7.
    Zimmermann H (2006) Nucleotide signaling in nervous system development. Pflugers Arch 452:573–588PubMedGoogle Scholar
  8. 8.
    Dale N (2008) Dynamic ATP signalling and neural development. J Physiol 586:2429–2436PubMedGoogle Scholar
  9. 9.
    Igusa Y (1988) Adenosine 5′-triphosphate activates acetylcholine receptor channels in cultured Xenopus myotomal muscle cells. J Physiol 405:169–185PubMedGoogle Scholar
  10. 10.
    Akasu T, Hirai K, Koketsu K (1981) Increase of acetylcholine-receptor sensitivity by adenosine triphosphate: a novel action of ATP on ACh-sensitivity. Br J Pharmacol 74:505–507PubMedGoogle Scholar
  11. 11.
    Fu WM (1995) Regulatory role of ATP at developing neuromuscular junctions. Prog Neurobiol 47:31–44PubMedGoogle Scholar
  12. 12.
    Fu WM, Poo MM (1991) ATP potentiates spontaneous transmitter release at developing neuromuscular synapses. Neuron 6:837–843PubMedGoogle Scholar
  13. 13.
    Fu WM (1994) Potentiation by ATP of the postsynaptic acetylcholine response at developing neuromuscular synapses in Xenopus cell cultures. J Physiol 477:449–458PubMedGoogle Scholar
  14. 14.
    Fu WM, Huang FL (1994) Potentiation by endogenously released ATP of spontaneous transmitter secretion at developing neuromuscular synapses in Xenopus cell cultures. Br J Pharmacol 111:880–886PubMedGoogle Scholar
  15. 15.
    Lu B, Fu WM (1995) Regulation of postsynaptic responses by calcitonin gene related peptide and ATP at developing neuromuscular junctions. Can J Physiol Pharmacol 73:1050–1056PubMedGoogle Scholar
  16. 16.
    Fu WM, Chen YH, Lee KF, Liou JC (1997) Regulation of quantal transmitter secretion by ATP and protein kinases at developing neuromuscular synapses. Eur J Neurosci 9:676–685PubMedGoogle Scholar
  17. 17.
    Bogdanov YD, Dale L, King BF, Whittock N, Burnstock G (1997) Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos. J Biol Chem 272:12583–12590PubMedGoogle Scholar
  18. 18.
    Burnstock G (1996) P2 purinoceptors: historical perspective and classification. In: Chadwick DJ, Goode JA (eds) P2 purinoceptors: localization, function and transduction mechanisms. Ciba Foundation Symposium vol 198. Wiley, Chichester, pp 1–29Google Scholar
  19. 19.
    Gerhart J, Danilchik M, Doniach T, Roberts S, Rowning B, Stewart R (1989) Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development. Development 107(Suppl):37–51Google Scholar
  20. 20.
    Dale N, Gilday D (1996) Regulation of rhythmic movements by purinergic neurotransmitters in frog embryos. Nature 383:259–263PubMedGoogle Scholar
  21. 21.
    Brown P, Dale N (2000) Adenosine A1 receptors modulate high voltage-activated Ca2+ currents and motor pattern generation in the Xenopus embryo. J Physiol 525:655–667PubMedGoogle Scholar
  22. 22.
    Dale N (1998) Delayed production of adenosine underlies temporal modulation of swimming in frog embryo. J Physiol 511:265–272PubMedGoogle Scholar
  23. 23.
    Devader C, Webb RJ, Thomas GM, Dale L (2006) Xenopus apyrase (xapy), a secreted nucleotidase that is expressed during early development. Gene 367:135–141PubMedGoogle Scholar
  24. 24.
    Laasberg T (1990) Ca2+-mobilizing receptors of gastrulating chick embryo. Comp Biochem Physiol C 97:9–12PubMedGoogle Scholar
  25. 25.
    Hilfer SR, Palmatier BY, Fithian EM (1977) Precocious evagination of the embryonic chick thyroid in ATP-containing medium. J Embryol Exp Morphol 42:163–175Google Scholar
  26. 26.
    Nakaoka Y, Yamashita M (1995) Ca2+ responses to acetylcholine and adenosine triphosphate in the otocyst of chick embryo. J Neurobiol 28:23–34PubMedGoogle Scholar
  27. 27.
    Häggblad J, Heilbronn E (1988) P2-purinoceptor-stimulated phosphoinositide turnover in chick myotubes. Calcium mobilization and the role of guanyl nucleotide-binding proteins. FEBS Lett 235:133–136PubMedGoogle Scholar
  28. 28.
    Lohmann F, Drews U, Donié F, Reiser G (1991) Chick embryo muscarinic and purinergic receptors activate cytosolic Ca2+ via phosphatidylinositol metabolism. Exp Cell Res 197:326–329PubMedGoogle Scholar
  29. 29.
    Meyer MP, Clarke JDW, Patel K, Townsend-Nicholson A, Burnstock G (1999) Selective expression of purinoceptor cP2Y1 suggests a role for nucleotide signalling in development of the chick embryo. Dev Dyn 214:152–158PubMedGoogle Scholar
  30. 30.
    Adair TH, Montani JP, Strick DM, Guyton AC (1989) Vascular development in chick embryos: a possible role for adenosine. Am J Physiol 256:H240–H246PubMedGoogle Scholar
  31. 31.
    Fraser RA, Ellis EM, Stalker AL (1979) Experimental angiogenesis in the chorio-allantoic membrane. Bibl Anat 18:25–27PubMedGoogle Scholar
  32. 32.
    Teuscher E, Weidlich V (1985) Adenosine nucleotides, adenosine and adenine as angiogenesis factors. Biomed Biochim Acta 44:493–495PubMedGoogle Scholar
  33. 33.
    Dusseau JW, Hutchins PM, Malbasa DS (1986) Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane. Circ Res 59:163–170PubMedGoogle Scholar
  34. 34.
    Kubo Y (1991) Properties of ionic currents induced by external ATP in a mouse mesodermal stem cell line. J Physiol 442:691–710PubMedGoogle Scholar
  35. 35.
    Kubo Y (1991) Electrophysiological and immunohistochemical analysis of muscle differentiation in a mouse mesodermal stem cell line. J Physiol 442:711–741PubMedGoogle Scholar
  36. 36.
    Beaudoin AR (1976) Effect of adenosine triphosphate and adenosine diphosphate on the teratogenic action of Trypan blue in rats. Neonatology 28:133–139Google Scholar
  37. 37.
    Gordon HW, Tkaczyk W, Peer LA, Bernhard WG (1963) The effect of adenosine triphosphate and its decomposition products on cortisone induced teratology. J Embryol Exp Morphol 11:475–482PubMedGoogle Scholar
  38. 38.
    Smuts MS (1981) Rapid nasal pit formation in mouse embryos stimulated by ATP-containing medium. J Exp Zool 216:409–414PubMedGoogle Scholar
  39. 39.
    Nakano H, Shimada A, Imai K, Takahashi T, Hashizume K (2003) ATP-evoked increase in intracellular calcium via the P2Y receptor in proliferating bovine trophoblast cells. Cell Tissue Res 313:227–236PubMedGoogle Scholar
  40. 40.
    Petrungaro S, Salustri A, Siracusa G (1986) Adenosine potentiates the delaying effect of dbcAMP on meiosis resumption in denuded mouse oocytes. Cell Biol Int Rep 10:993PubMedGoogle Scholar
  41. 41.
    Knudsen TB, Elmer WA (1987) Evidence for negative control of growth by adenosine in the mammalian embryo: induction of Hmx/+ mutant limb outgrowth by adenosine deaminase. Differentiation 33:270–279PubMedGoogle Scholar
  42. 42.
    Nureddin A, Epsaro E, Kiessling AA (1990) Purines inhibit the development of mouse embryos in vitro. J Reprod Fertil 90:455–464PubMedGoogle Scholar
  43. 43.
    Loutradis D, John D, Kiessling AA (1987) Hypoxanthine causes a 2-cell block in random-bred mouse embryos. Biol Reprod 37:311–316PubMedGoogle Scholar
  44. 44.
    Fissore R, O’Keefe S, Kiessling AA (1992) Purine-induced block to mouse embryo cleavage is reversed by compounds that elevate cyclic adenosine monophosphate. Biol Reprod 47:1105–1112PubMedGoogle Scholar
  45. 45.
    Chechik BE, Sengupta S, Hibi T, Fernandes B (1985) Immunomorphological localization of adenosine deaminase in rat tissues during ontogeny. Histochem J 17:153–170PubMedGoogle Scholar
  46. 46.
    Jenuth JP, Mably ER, Snyder FF (1996) Modelling of purine nucleoside metabolism during mouse embryonic development: relative routes of adenosine, deoxyadenosine, and deoxyguanosine metabolism. Biochem Cell Biol 74:219–225PubMedGoogle Scholar
  47. 47.
    Franco R, Casado V, Ciruela F, Saura C, Mallol J, Canela EI, Lluis C (1997) Cell surface adenosine deaminase: much more than an ectoenzyme. Prog Neurobiol 52:283–294PubMedGoogle Scholar
  48. 48.
    Schachter JB, Sromek SM, Nicholas RA, Harden TK (1997) HEK293 human embryonic kidney cells endogenously express the P2Y1 and P2Y2 receptors. Neuropharmacology 36:1181–1187PubMedGoogle Scholar
  49. 49.
    Cooper J, Hill SJ, Alexander SP (1997) An endogenous A2B adenosine receptor coupled to cyclic AMP generation in human embryonic kidney (HEK 293) cells. Br J Pharmacol 122:546–550PubMedGoogle Scholar
  50. 50.
    Neary JT, McCarthy M, Kang Y, Zuniga S (1998) Mitogenic signaling from P1 and P2 purinergic receptors to mitogen-activated protein kinase in human fetal astrocyte cultures. Neurosci Lett 242:159–162PubMedGoogle Scholar
  51. 51.
    Fukuda S, Katoh S, Yamamoto K, Hashimoto M, Kitao M (1990) Correlation between levels of plasma adenosine triphosphate and stress to the fetus at delivery. Biol Neonate 57:150–154PubMedGoogle Scholar
  52. 52.
    Bynum JW (1980) Differential adenosine sensitivity in fibroblasts from different age donors. Exp Gerontol 15:217–225PubMedGoogle Scholar
  53. 53.
    Sobrevia L, Yudilevich DL, Mann GE (1997) Activation of A2-purinoceptors by adenosine stimulates l-arginine transport (system y+) and nitric oxide synthesis in human fetal endothelial cells. J Physiol 499:135–140PubMedGoogle Scholar
  54. 54.
    Blair TA, Parenti M, Murray TF (1989) Development of pharmacological sensitivity to adenosine analogs in embryonic chick heart: role of A1 adenosine receptors and adenylyl cyclase inhibition. Mol Pharmacol 35:661–670PubMedGoogle Scholar
  55. 55.
    Hatae J, Sperelakis N, Wahler GM (1989) Development of the response to adenosine during organ culture of young embryonic chick hearts. J Dev Physiol 11:342–345PubMedGoogle Scholar
  56. 56.
    Shryock J, Patel A, Belardinelli L, Linden J (1989) Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart. Am J Physiol 256:H321–H327PubMedGoogle Scholar
  57. 57.
    Liang BT, Haltiwanger B (1995) Adenosine A2a and A2b receptors in cultured fetal chick heart cells. High- and low-affinity coupling to stimulation of myocyte contractility and cAMP accumulation. Circ Res 76:242–251PubMedGoogle Scholar
  58. 58.
    Egerman RS, Bissonnette JM, Hohimer AR (1993) The effects of centrally administered adenosine on fetal sheep heart rate accelerations. Am J Obstet Gynecol 169:866–869PubMedGoogle Scholar
  59. 59.
    Rivkees SA (1995) The ontogeny of cardiac and neural A1 adenosine receptor expression in rats. Brain Res Dev Brain Res 89:202–213PubMedGoogle Scholar
  60. 60.
    Hofman PL, Hiatt K, Yoder MC, Rivkees SA (1997) A1 adenosine receptors potently regulate heart rate in mammalian embryos. Am J Physiol 273:R1374–R1380PubMedGoogle Scholar
  61. 61.
    Weber RG, Jones CR, Lohse MJ, Palacios JM (1990) Autoradiographic visualization of A1 adenosine receptors in rat brain with [3H]8-cyclopentyl-1,3-dipropylxanthine. J Neurochem 54:1344–1353PubMedGoogle Scholar
  62. 62.
    Reppert SM, Weaver DR, Stehle JH, Rivkees SA (1991) Molecular cloning and characterization of a rat A1-adenosine receptor that is widely expressed in brain and spinal cord. Mol Endocrinol 5:1037–1048PubMedGoogle Scholar
  63. 63.
    Cothran DL, Lloyd TR, Taylor H, Linden J, Matherne GP (1995) Ontogeny of rat myocardial A1 adenosine receptors. Biol Neonate 68:111–118PubMedGoogle Scholar
  64. 64.
    Yoneyama Y, Power GG (1992) Plasma adenosine and cardiovascular responses to dipyridamole in fetal sheep. J Dev Physiol 18:203–209PubMedGoogle Scholar
  65. 65.
    Konduri GG, Woodard LL, Mukhopadhyay A, Deshmukh DR (1992) Adenosine is a pulmonary vasodilator in newborn lambs. Am Rev Respir Dis 146:670–676PubMedGoogle Scholar
  66. 66.
    Koos BJ, Mason BA, Ducsay CA (1993) Cardiovascular responses to adenosine in fetal sheep: autonomic blockade. Am J Physiol 264:H526–H532PubMedGoogle Scholar
  67. 67.
    Mason BA, Ogunyemi D, Punla O, Koos BJ (1993) Maternal and fetal cardiorespiratory responses to adenosine in sheep. Am J Obstet Gynecol 168:1558–1561PubMedGoogle Scholar
  68. 68.
    Bogdanov YD, Wildman SS, Clements MP, King BF, Burnstock G (1998) Molecular cloning and characterization of rat P2Y4 nucleotide receptor. Special report. Br J Pharmacol 124:428–430PubMedGoogle Scholar
  69. 69.
    Ruppelt A, Liang BT, Soto F (1999) Cloning, functional characterization and developmental expression of a P2X receptor from chick embryo. Prog Brain Res 120:81–90PubMedGoogle Scholar
  70. 70.
    Kolb HA, Wakelam MJ (1983) Transmitter-like action of ATP on patched membranes of cultured myoblasts and myotubes. Nature 303:621–623PubMedGoogle Scholar
  71. 71.
    Häggblad J, Eriksson H, Heilbronn E (1985) ATP-induced cation influx in myotubes is additive to cholinergic agonist action. Acta Physiol Scand 125:389–393PubMedGoogle Scholar
  72. 72.
    Häggblad J, Heilbronn E (1987) Externally applied adenosine-5′-triphosphate causes inositol triphosphate accumulation in cultured chick myotubes. Neurosci Lett 74:199–204PubMedGoogle Scholar
  73. 73.
    Eriksson H, Heilbronn E (1989) Extracellularly applied ATP alters the calcium flux through dihydropyridine-sensitive channels in cultured chick myotubes. Biochem Biophys Res Commun 159:878–885PubMedGoogle Scholar
  74. 74.
    Hume RI, Hönig MG (1986) Excitatory action of ATP on embryonic chick muscle. J Neurosci 6:681–690PubMedGoogle Scholar
  75. 75.
    Hume RI, Thomas SA (1988) Multiple actions of adenosine 5′-triphosphate on chick skeletal muscle. J Physiol 406:503–524PubMedGoogle Scholar
  76. 76.
    Thomas SA, Hume RI (1990) Permeation of both cations and anions through a single class of ATP-activated ion channels in developing chick skeletal muscle. J Gen Physiol 95:569–590PubMedGoogle Scholar
  77. 77.
    Thomas SA, Hume RI (1990) Irreversible desensitization of ATP responses in developing chick skeletal muscle. J Physiol 430:373–388PubMedGoogle Scholar
  78. 78.
    Thomas SA, Zawisa MJ, Lin X, Hume RI (1991) A receptor that is highly specific for extracellular ATP in developing chick skeletal muscle in vitro. Br J Pharmacol 103:1963–1969PubMedGoogle Scholar
  79. 79.
    Wells DG, Zawisa MJ, Hume RI (1995) Changes in responsiveness to extracellular ATP in chick skeletal muscle during development and upon denervation. Dev Biol 172:585–590PubMedGoogle Scholar
  80. 80.
    Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88:49–92Google Scholar
  81. 81.
    Mehul B, Doyennette-Moyne MA, Aubery M, Codogno P, Mannherz HG (1992) Enzymatic activity and in vivo distribution of 5′-nucleotidase, an extracellular matrix binding glycoprotein, during the development of chicken striated muscle. Exp Cell Res 203:62–71PubMedGoogle Scholar
  82. 82.
    Soto F, Krause U, Borchardt K, Ruppelt A (2003) Cloning, tissue distribution and functional characterization of the chicken P2X1 receptor. FEBS Lett 533:54–58PubMedGoogle Scholar
  83. 83.
    Ruppelt A, Ma W, Borchardt K, Silberberg SD, Soto F (2001) Genomic structure, developmental distribution and functional properties of the chicken P2X5 receptor. J Neurochem 77:1256–1265PubMedGoogle Scholar
  84. 84.
    Henning RH, Nelemans A, Van den Akker J, Den Hertog A (1992) The nucleotide receptors on mouse C2C12 myotubes. Br J Pharmacol 106:853–858PubMedGoogle Scholar
  85. 85.
    Henning RH, Duin M, Den Hertog A, Nelemans A (1993) Activation of the phospholipase C pathway by ATP is mediated exclusively through nucleotide type P2-purinoceptors in C2C12 myotubes. Br J Pharmacol 110:747–752PubMedGoogle Scholar
  86. 86.
    Henning RH, Duin M, Den Hertog A, Nelemans A (1993) Characterization of P2-purinoceptor mediated cyclic AMP formation in mouse C2C12 myotubes. Br J Pharmacol 110:133–138PubMedGoogle Scholar
  87. 87.
    Henning RH, Duin M, van Popta JP, Nelemans A, Den Hertog A (1996) Different mechanisms of Ca2+-handling following nicotinic acetylcholine receptor stimulation, P2U-purinoceptor stimulation and K+-induced depolarization in C2C12 myotubes. Br J Pharmacol 117:1785–1791PubMedGoogle Scholar
  88. 88.
    Tassin AM, Haggblad J, Heilbronn E (1990) Receptor-triggered polyphosphoinositide turnover produces less cytosolic free calcium in cultured dysgenic myotubes than in normal myotubes. Muscle Nerve 13:142–145PubMedGoogle Scholar
  89. 89.
    Collet C, Strube C, Csernoch L, Mallouk N, Ojeda C, Allard B, Jacquemond V (2002) Effects of extracellular ATP on freshly isolated mouse skeletal muscle cells during pre-natal and post-natal development. Pflugers Arch 443:771–778PubMedGoogle Scholar
  90. 90.
    May C, Weigl L, Karel A, Hohenegger M (2006) Extracellular ATP activates ERK1/ERK2 via a metabotropic P2Y1 receptor in a Ca2+ independent manner in differentiated human skeletal muscle cells. Biochem Pharmacol 71:1497–1509PubMedGoogle Scholar
  91. 91.
    Ryten M, Hoebertz A, Burnstock G (2001) Sequential expression of three receptor subtypes for extracellular ATP in developing rat skeletal muscle. Dev Dyn 221:331–341PubMedGoogle Scholar
  92. 92.
    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 158:345–355PubMedGoogle Scholar
  93. 93.
    Ryten M, Koshi R, Knight GE, Turmaine M, Dunn PM, Cockayne DA, Ford APDW, Burnstock G (2007) Abnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor. Neuroscience 148:700–711PubMedGoogle Scholar
  94. 94.
    Choi HB, Hong SH, Ryu JK, Kim SU, McLarnon JG (2003) Differential activation of subtype purinergic receptors modulates Ca2+ mobilization and COX-2 in human microglia. Glia 43:95–103PubMedGoogle Scholar
  95. 95.
    Ling KK, Siow NL, Choi RC, Tsim KW (2005) ATP potentiates the formation of AChR aggregate in the co-culture of NG108–15 cells with C2C12 myotubes. FEBS Lett 579:2469–2474PubMedGoogle Scholar
  96. 96.
    Morgan PF, Montgomery P, Marangos PJ (1987) Ontogenetic profile of the adenosine uptake sites in rat forebrain. J Neurochem 49:852–855PubMedGoogle Scholar
  97. 97.
    Morgan PF, Deckert J, Nakajima T, Daval JL, Marangos PJ (1990) Late ontogenetic development of adenosine A1 receptor coupling to associated G-proteins in guinea pig cerebellum but not forebrain. Mol Cell Biochem 92:169–176PubMedGoogle Scholar
  98. 98.
    Nicolas F, Daval JL (1993) Expression of adenosine A1 receptors in cultured neurons from fetal rat brain. Synapse 14:96–99PubMedGoogle Scholar
  99. 99.
    Marangos PJ, Patel J, Stivers J (1982) Ontogeny of adenosine binding sites in rat forebrain and cerebellum. J Neurochem 39:267–270PubMedGoogle Scholar
  100. 100.
    Geiger JD, LaBella FS, Nagy JI (1984) Ontogenesis of adenosine receptors in the central nervous system of the rat. Brain Res 13:97–104Google Scholar
  101. 101.
    Weaver DR (1996) A1-adenosine receptor gene expression in fetal rat brain. Brain Res Dev Brain Res 94:205–223PubMedGoogle Scholar
  102. 102.
    Deckert J, Morgan PF, Daval JL, Nakajima T, Marangos PJ (1988) Ontogeny of adenosine uptake sites in guinea pig brain: differential profile of [3H]nitrobenzylthioinosine and [3H]dipyridamole binding sites. Brain Res 470:313–316PubMedGoogle Scholar
  103. 103.
    León D, Albasanz JL, Ruiz MA, Fernandez M, Martin M (2002) Adenosine A1 receptor down-regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats. J Neurochem 82:625–634PubMedGoogle Scholar
  104. 104.
    Reynolds JD, Brien JF (1995) The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated glutamate release in the hippocampus of the fetal and adult guinea pig. Alcohol 12:151–157PubMedGoogle Scholar
  105. 105.
    Schoen SW, Leutenecker B, Kreutzberg GW, Singer W (1990) Ocular dominance plasticity and developmental changes of 5′-nucleotidase distributions in the kitten visual cortex. J Comp Neurol 296:379–392PubMedGoogle Scholar
  106. 106.
    Schoen SW, Kreutzberg GW, Singer W (1993) Cytochemical redistribution of 5′-nucleotidase in the developing cat visual cortex. Eur J Neurosci 5:210–222PubMedGoogle Scholar
  107. 107.
    Mishra OP, Wagerle LC, Delivoria Papadopoulos M (1988) 5’-Nucleotidase and adenosine deaminase in developing fetal guinea pig brain and the effect of maternal hypoxia. Neurochem Res 13:1055–1060PubMedGoogle Scholar
  108. 108.
    Geiger JD, Nagy JI (1987) Ontogenesis of adenosine deaminase activity in rat brain. J Neurochem 48:147–153PubMedGoogle Scholar
  109. 109.
    Senba E, Daddona PE, Nagy JI (1987) Transient expression of adenosine deaminase in facial and hypoglossal motoneurons of the rat during development. J Comp Neurol 255:217–230PubMedGoogle Scholar
  110. 110.
    Senba E, Daddona PE, Nagy JI (1987) Development of adenosine deaminase-immunoreactive neurons in the rat brain. Brain Res 428:59–71PubMedGoogle Scholar
  111. 111.
    Senba E, Daddona PE, Nagy JI (1987) Adenosine deaminase-containing neurons in the olfactory system of the rat during development. Brain Res Bull 18:635–648PubMedGoogle Scholar
  112. 112.
    Yoshioka T, Inoata K, Tanaka O (1987) Cytochemistry of Ca2+-ATPase in the rat spinal cord during embryonic development. Acta Histochem Cytochem 20:511–526Google Scholar
  113. 113.
    Yoshioka T (1989) Histochemical examination of adenosine nucleotidases in the developing rat spinal cord: possible involvement in enzymatic chain of ATP degradation. Acta Histochem Cytochem 22:685–694Google Scholar
  114. 114.
    Salter MW, Hicks JL (1995) ATP causes release of intracellular Ca2+ via the phospholipase Cβ/IP3 pathway in astrocytes from the dorsal spinal cord. J Neurosci 15:2961–2971PubMedGoogle Scholar
  115. 115.
    Kidd EJ, Miller KJ, Sansum AJ, Humphrey PPA (1998) Evidence for P2X3 receptors in the developing rat brain. Neuroscience 87:533–539PubMedGoogle Scholar
  116. 116.
    Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology 36:1277–1283PubMedGoogle Scholar
  117. 117.
    Narcisse L, Scemes E, Zhao Y, Lee SC, Brosnan CF (2005) The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes. Glia 49:245–258PubMedGoogle Scholar
  118. 118.
    Khakh BS, Smith WB, Chiu CS, Ju D, Davidson N, Lester HA (2001) Activation-dependent changes in receptor distribution and dendritic morphology in hippocampal neurons expressing P2X2-green fluorescent protein receptors. Proc Natl Acad Sci USA 98:5288–5293PubMedGoogle Scholar
  119. 119.
    García-Lecea M, Sen RP, Soto F, Miras-Portugal MT, Castro E (2001) P2 receptors in cerebellar neurons: molecular diversity of ionotropic ATP receptors in Purkinje cells. Drug Dev Res 52:104–113Google Scholar
  120. 120.
    Maric D, Maric I, Chang YH, Barker JL (2000) Stereotypical physiological properties emerge during early neuronal and glial lineage development in the embryonic rat neocortex. Cereb Cortex 10:729–747PubMedGoogle Scholar
  121. 121.
    Cheung K-K, Burnstock G (2002) Localisation of P2X3 and co-expression with P2X2 receptors during rat embryonic neurogenesis. J Comp Neurol 443:368–382PubMedGoogle Scholar
  122. 122.
    Cheung K-K, Ryten M, Burnstock G (2003) Abundant and dynamic expression of G protein-coupled P2Y receptors in mammalian development. Dev Dyn 228:254–266PubMedGoogle Scholar
  123. 123.
    Zhu Y, Kimelberg HK (2001) Developmental expression of metabotropic P2Y1 and P2Y2 receptors in freshly isolated astrocytes from rat hippocampus. J Neurochem 77:530–541PubMedGoogle Scholar
  124. 124.
    Cheung K-K, Chan WY, Burnstock G (2005) Expression of P2X receptors during rat brain development and their inhibitory role on motor axon outgrowth in neural tube explant cultures. Neuroscience 133:937–945PubMedGoogle Scholar
  125. 125.
    Boldogköi Z, Schütz B, Sallach J, Zimmer A (2002) P2X3 receptor expression at early stage of mouse embryogenesis. Mech Dev 118:255–260PubMedGoogle Scholar
  126. 126.
    Jo YH, Role LW (2002) Cholinergic modulation of purinergic and GABAergic co-transmission at in vitro hypothalamic synapses. J Neurophysiol 88:2501–2508PubMedGoogle Scholar
  127. 127.
    Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661PubMedGoogle Scholar
  128. 128.
    Ryu JK, Choi HB, Hatori K, Heisel RL, Pelech SL, McLarnon JG, Kim SU (2003) Adenosine triphosphate induces proliferation of human neural stem cells: role of calcium and p70 ribosomal protein S6 kinase. J Neurosci Res 72:352–362PubMedGoogle Scholar
  129. 129.
    Dale N (2002) Resetting intrinsic purinergic modulation of neural activity: an associative mechanism? J Neurosci 22:10461–10469PubMedGoogle Scholar
  130. 130.
    Norton WHJ, Rohr KB, Burnstock G (2000) Embryonic expression of a P2X3 receptor encoding gene in zebrafish. Mech Dev 99:149–152PubMedGoogle Scholar
  131. 131.
    Meghji P, Tuttle JB, Rubio R (1989) Adenosine formation and release by embryonic chick neurons and glia in cell culture. J Neurochem 53:1852–1860PubMedGoogle Scholar
  132. 132.
    Thampy KG, Barnes EM Jr (1983) Adenosine transport by cultured glial cells from chick embryo brain. Arch Biochem Biophys 220:340–346PubMedGoogle Scholar
  133. 133.
    Thampy KG, Barnes EM Jr (1983) Adenosine transport by primary cultures of neurons from chick embryo brain. J Neurochem 40:874–879PubMedGoogle Scholar
  134. 134.
    Barnes EM Jr, Thampy KG (1982) Subclasses of adenosine receptors in brain membranes from adult tissue and from primary cultures of chick embryo. J Neurochem 39:647–652PubMedGoogle Scholar
  135. 135.
    Zhang Z, Galileo DS (1998) Widespread programme death in early developing chick optic tectum. Neuroreport 9:2797–2801PubMedGoogle Scholar
  136. 136.
    Di Virgilio F, Zanovello P, Zambon A, Bronte V, Pizzo P, Murgia M (1995) Cell membrane receptors for extracelluar ATP: a new family of apoptosis-signalling molecules. Fundam Clin Immunol 3:80–81Google Scholar
  137. 137.
    Di Virgilio F, Chiozzi P, Falzoni S, Ferrari D, Sanz JM, Venketaraman V, Baricordi OR (1998) Cytolytic P2X purinoceptors. Cell Death Differ 5:191–199PubMedGoogle Scholar
  138. 138.
    Wakade TD, Palmer KC, McCauley R, Przywara DA, Wakade AR (1995) Adenosine-induced apoptosis in chick embryonic sympathetic neurons: a new physiological role for adenosine. J Physiol 488:123–138PubMedGoogle Scholar
  139. 139.
    Abe Y, Sorimachi M, Itoyama Y, Furukawa K, Akaike N (1995) ATP responses in the embryo chick ciliary ganglion cells. Neuroscience 64:547–551PubMedGoogle Scholar
  140. 140.
    Labrakakis C, Gerstner E, MacDermott AB (2000) Adenosine triphosphate-evoked currents in cultured dorsal root ganglion neurons obtained from rat embryos: desensitization kinetics and modulation of glutamate release. Neuroscience 101:1117–1126PubMedGoogle Scholar
  141. 141.
    Kulkarni JS, Przywara DA, Wakade TD (1998) Adenosine induces apoptosis by inhibiting mRNA and protein synthesis in chick embryonic sympathetic neurons. Neurosci Lett 248:187–190PubMedGoogle Scholar
  142. 142.
    Nakatsuka T, Mena N, Ling J, Gu JG (2001) Depletion of substance P from rat primary sensory neurons by ATP, an implication of P2X receptor-mediated release of substance P. Neuroscience 107:293–300PubMedGoogle Scholar
  143. 143.
    Ruan H-Z, Moules E, Burnstock G (2004) Changes in P2X purinoceptors in sensory ganglia of the mouse during embryonic and postnatal development. Histochem Cell Biol 122:539–551PubMedGoogle Scholar
  144. 144.
    Huang H, Wu X, Nicol GD, Meller S, Vasko MR (2003) ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors. J Pharmacol Exp Ther 306:1137–1144PubMedGoogle Scholar
  145. 145.
    Dunn PM, Gever J, Ruan H-Z, Burnstock G (2005) Developmental changes in heteromeric P2X2/3 receptor expression in rat sympathetic ganglion neurons. Dev Dyn 234:505–511PubMedGoogle Scholar
  146. 146.
    Molliver DC, Wright DE, Leitner ML, Parsadanian AS, Doster K, Wen D, Yan Q, Snider WD (1997) IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron 19:849–861PubMedGoogle Scholar
  147. 147.
    Allgaier C, Wellmann H, Schobert A, von Kügelgen I (1995) Cultured chick sympathetic neurons: modulation of electrically evoked noradrenaline release by P2-purinoceptors. Naunyn Schmiedebergs Arch Pharmacol 352:17–24PubMedGoogle Scholar
  148. 148.
    Allgaier C, Wellmann H, Schobert A, Kurz G, von Kügelgen I (1995) Cultured chick sympathetic neurons: ATP-induced noradrenaline release and its blockade by nicotinic receptor antagonists. Naunyn Schmiedebergs Arch Pharmacol 352:25–30PubMedGoogle Scholar
  149. 149.
    Stellwagen D, Shatz CJ (2002) An instructive role for retinal waves in the development of retinogeniculate connectivity. Neuron 33:357–367PubMedGoogle Scholar
  150. 150.
    Syed MM, Lee S, Zheng J, Zhou ZJ (2004) Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina. J Physiol 560:533–549PubMedGoogle Scholar
  151. 151.
    Sugioka M, Fukuda Y, Yamashita M (1996) Ca2+ responses to ATP via purinoceptors in the early embryonic chick retina. J Physiol 493:855–863PubMedGoogle Scholar
  152. 152.
    Sakai Y, Fukuda Y, Yamashita M (1996) Muscarinic and purinergic Ca2+ mobilisation in the neural retina of early embryonic chick. Int J Dev Neurosci 14:691–699Google Scholar
  153. 153.
    Sugioka M, Zhou WL, Hofmann HD, Yamashita M (1999) Involvement of P2 purinoceptors in the regulation of DNA synthesis in the neural retina of chick embryo. Int J Dev Neurosci 17:135–144PubMedGoogle Scholar
  154. 154.
    Yamashita M, Sugioka M (1998) Calcium mobilization systems during neurogenesis. News Physiol Sci 13:75–79PubMedGoogle Scholar
  155. 155.
    Sanches G, de Alencar LS, Ventura AL (2002) ATP induces proliferation of retinal cells in culture via activation of PKC and extracellular signal-regulated kinase cascade. Int J Dev Neurosci 20:21–27PubMedGoogle Scholar
  156. 156.
    Burgos JS, Barat A, Ramirez G (2000) Guanine nucleotides block agonist-driven 45Ca2+ influx in chick embryo retinal explants. Neuroreport 11:2303–2305PubMedGoogle Scholar
  157. 157.
    Paes de Carvalho R, De Mello FG (1982) Adenosine-elicited accumulation of adenosine 3′, 5′-cyclic monophosphate in the chick embryo retina. J Neurochem 38:493–500PubMedGoogle Scholar
  158. 158.
    Paes de Carvalho R, De Mello FG (1985) Expression of A1 adenosine receptors modulating dopamine-dependent cyclic AMP accumulation in the chick embryo retina. J Neurochem 44:845–851PubMedGoogle Scholar
  159. 159.
    de Mello MC, Ventura AL, Paes de Carvalho R, Klein WL, De Mello FG (1982) Regulation of dopamine- and adenosine-dependent adenylate cyclase systems of chicken embryo retina cells in culture. Proc Natl Acad Sci USA 79:5708–5712PubMedGoogle Scholar
  160. 160.
    Paes de Carvalho R, Braas KM, Alder R, Snyder SH (1992) Developmental regulation of adenosine A1 receptors, uptake sites and endogenous adenosine in the chick retina. Brain Res Dev Brain Res 70:87–95Google Scholar
  161. 161.
    Massé K, Bhamra S, Eason R, Dale N, Jones EA (2007) Purine-mediated signalling triggers eye development. Nature 449:1058–1062PubMedGoogle Scholar
  162. 162.
    Ito S, Ohta T, Kimura A, Ohga A (1988) Development of substance P- and vasoactive intestinal polypeptide-containing neurones in the rat stomach. Q J Exp Physiol 73:729–736PubMedGoogle Scholar
  163. 163.
    Gershon MD, Thompson EB (1973) The maturation of neuromuscular function in a multiply innervated structure: development of the longitudinal smooth muscle of the foetal mammalian gut and its cholinergic excitatory, adrenergic inhibitory, and non-adrenergic inhibitory innervation. J Physiol 234:257–277PubMedGoogle Scholar
  164. 164.
    Crowe R, Burnstock G (1981) Perinatal development of quinacrine-positive neurons in the rabbit gastrointestinal tract. J Auton Nerv Syst 4:217–230PubMedGoogle Scholar
  165. 165.
    Miyazaki H, Ohga A, Saito K (1982) Development of motor response to intramural nerve stimulation and to drugs in rat small intestine. Br J Pharmacol 76:531–540PubMedGoogle Scholar
  166. 166.
    Zagorodnyuk V, Hoyle CHV, Burnstock G (1993) An electrophysiological study of developmental changes in the innervation of the guinea-pig taenia coli. Pflugers Arch 423:427–433PubMedGoogle Scholar
  167. 167.
    Clunes MT, Collett A, Baines DL, Bovell DL, Murphie H, Inglis SK, McAlroy HL, Olver RE, Wilson SM (1998) Culture substrate-specific expression of P2Y2 receptors in distal lung epithelial cells isolated from foetal rats. Br J Pharmacol 124:845–847PubMedGoogle Scholar
  168. 168.
    Barker PM, Gatzy JT (1998) Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung. Pediatr Res 43:652–659PubMedGoogle Scholar
  169. 169.
    Konduri GG, Gervasio CT, Theodorou AA (1993) Role of adenosine triphosphate and adenosine in oxygen-induced pulmonary vasodilation in fetal lambs. Pediatr Res 33:533–539PubMedGoogle Scholar
  170. 170.
    Konduri GG, Mital S, Gervasio CT, Rotta AT, Forman K (1997) Purine nucleotides contribute to pulmonary vasodilation caused by birth-related stimuli in the ovine fetus. Am J Physiol 272:H2377–H2384PubMedGoogle Scholar
  171. 171.
    Konduri GG, Forman K, Mital S (2000) Characterization of purine receptors in fetal lamb pulmonary circulation. Pediatr Res 47:114–120PubMedGoogle Scholar
  172. 172.
    Brouns I, Van Genechten J, Hayashi H, Gajda M, Gomi T, Burnstock G, Timmermans J-P, Adriaensen D (2003) Dual sensory innervation of pulmonary neuroepithelial bodies. Am J Respir Cell Mol Biol 28:275–285PubMedGoogle Scholar
  173. 173.
    O’Reilly BA, Kosaka AH, Chang TK, Ford AP, Popert R, Rymer JM, McMahon SB (2001) A quantitative analysis of purinoceptor expression in human fetal and adult bladders. J Urol 165:1730–1734PubMedGoogle Scholar
  174. 174.
    Thiruchelvam N, Wu C, David A, Woolf AS, Cuckow PM, Fry CH (2003) Neurotransmission and viscoelasticity in the ovine fetal bladder after in utero bladder outflow obstruction. Am J Physiol Regul Integr Comp Physiol 284:R1296–R1305PubMedGoogle Scholar
  175. 175.
    Housley GD, Marcotti W, Navaratnam D, Yamoah EN (2006) Hair cells: beyond the transducer. J Membr Biol 209:89–118PubMedGoogle Scholar
  176. 176.
    Nikolic P, Housley GD, Luo L, Ryan AF, Thorne PR (2001) Transient expression of P2X1 receptor subunits of ATP-gated ion channels in the developing rat cochlea. Brain Res Dev Brain Res 126:173–182PubMedGoogle Scholar
  177. 177.
    Huang LC, Greenwood D, Thorne PR, Housley GD (2005) Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea. J Comp Neurol 484:133–143PubMedGoogle Scholar
  178. 178.
    Huang LC, Ryan AF, Cockayne DA, Housley GD (2006) Developmentally regulated expression of the P2X3 receptor in the mouse cochlea. Histochem Cell Biol 125:681–692PubMedGoogle Scholar
  179. 179.
    Hatori M, Teixeira CC, Debolt K, Pacifici M, Shapiro IM (1995) Adenine nucleotide metabolism by chondrocytes in vitro: role of ATP in chondrocyte maturation and matrix mineralization. J Cell Physiol 165:468–474PubMedGoogle Scholar
  180. 180.
    Hung CT, Allen FD, Mansfield KD, Shapiro IM (1997) Extracellular ATP modulates [Ca2+]i in retinoic acid-treated embryonic chondrocytes. Am J Physiol 272:C1611–C1617PubMedGoogle Scholar
  181. 181.
    Fredholm BB, Lerner U (1982) Metabolism of adenosine and 2′-deoxy-adenosine by fetal mouse calvaria in culture. Med Biol 60:267–271PubMedGoogle Scholar
  182. 182.
    Modderman WE, Weidema AF, Vrijheid-Lammers T, Wassenaar AM, Nijweide PJ (1994) Permeabilization of cells of hemopoietic origin by extracellular ATP4−: elimination of osteoclasts, macrophages, and their precursors from isolated bone cell populations and fetal bone rudiments. Calcif Tissue Int 55:141–150PubMedGoogle Scholar
  183. 183.
    Hsu HH (1983) Purification and partial characterization of ATP pyrophosphohydrolase from fetal bovine epiphyseal cartilage. J Biol Chem 258:3463–3468PubMedGoogle Scholar
  184. 184.
    Pác L (1984) Contribution to ontogenesis of Merkel cells. Z Mikrosk Anat Forsch 98:36–48PubMedGoogle Scholar
  185. 185.
    Burnstock G, Wood JN (1996) Purinergic receptors: their role in nociception and primary afferent neurotransmission. Curr Opin Neurobiol 6:526–532PubMedGoogle Scholar
  186. 186.
    Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156PubMedGoogle Scholar
  187. 187.
    Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638PubMedGoogle Scholar
  188. 188.
    Majumder P, Trujillo CA, Lopes CG, Resende RR, Gomes KN, Yuahasi KK, Britto LR, Ulrich H (2007) New insights into purinergic receptor signaling in neuronal differentiation, neuroprotection, and brain disorders. Purinergic Signal 3:317–331PubMedGoogle Scholar
  189. 189.
    McBurney MW (1993) P19 embryonal carcinoma cells. Int J Dev Biol 37:135–140PubMedGoogle Scholar
  190. 190.
    Resende RR, Majumder P, Gomes KN, Britto LR, Ulrich H (2007) P19 embryonal carcinoma cells as in vitro model for studying purinergic receptor expression and modulation of N-methyl-d-aspartate-glutamate and acetylcholine receptors during neuronal differentiation. Neuroscience 146:1169–1181PubMedGoogle Scholar
  191. 191.
    Resende RR, Britto LR, Ulrich H (2008) Pharmacological properties of purinergic receptors and their effects on proliferation and induction of neuronal differentiation of P19 embryonal carcinoma cells. Int J Dev Neurosci 26:763–777PubMedGoogle Scholar
  192. 192.
    Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438PubMedGoogle Scholar
  193. 193.
    Martins AH, Alves JM, Trujillo CA, Schwindt TT, Barnabé GF, Motta FL, Guimarães AO, Casarini DE, Mello LE, Pesquero JB, Ulrich H (2008) Kinin-B2 receptor expression and activity during differentiation of embryonic rat neurospheres. Cytometry A 73:361–368PubMedGoogle Scholar
  194. 194.
    Trujillo CA, Schwindt TT, Martins AH, Alves JM, Mello LE, Ulrich H (2009) Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics. Cytometry A 75:38–53PubMedGoogle Scholar
  195. 195.
    Schwindt TT, Trujillo CA, Negraes PD, Lameu C, Ulrich H (2010) Directed differentiation of neural progenitors into neurons is accompanied by altered expression of P2X purinergic receptors. J Mol Neurosci [Epub ahead of print, July 9]Google Scholar
  196. 196.
    da Silva RL, Resende RR, Ulrich H (2007) Alternative splicing of P2X6 receptors in developing mouse brain and during in vitro neuronal differentiation. Exp Physiol 92:139–145PubMedGoogle Scholar
  197. 197.
    Hofstetter CP, Holmstrom NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, Wiesenfeld-Hallin Z, Kurpad SN, Frisén J, Olson L (2005) Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 8:346–353PubMedGoogle Scholar
  198. 198.
    Kanemura Y, Mori H, Nakagawa A, Islam MO, Kodama E, Yamamoto A, Shofuda T, Kobayashi S, Miyake J, Yamazaki T, Hirano S, Yamasaki M, Okano H (2005) In vitro screening of exogenous factors for human neural stem/progenitor cell proliferation using measurement of total ATP content in viable cells. Cell Transplant 14:673–682PubMedGoogle Scholar
  199. 199.
    D’Ambrosi N, Murra B, Cavaliere F, Amadio S, Bernardi G, Burnstock G, Volonté C (2001) Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells. Neuroscience 108:527–534PubMedGoogle Scholar
  200. 200.
    Jia C, Doherty JP, Crudgington S, Hegg CC (2009) Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium. Neuroscience 163:120–128PubMedGoogle Scholar
  201. 201.
    Jia C, Hegg CC (2010) NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium. Neurobiol Dis 38:405–413PubMedGoogle Scholar
  202. 202.
    Hogg RC, Chipperfield H, Whyte KA, Stafford MR, Hansen MA, Cool SM, Nurcombe V, Adams DJ (2004) Functional maturation of isolated neural progenitor cells from the adult rat hippocampus. Eur J Neurosci 19:2410–2420PubMedGoogle Scholar
  203. 203.
    Shukla V, Zimmermann H, Wang L, Kettenmann H, Raab S, Hammer K, Sévigny J, Robson SC, Braun N (2005) Functional expression of the ecto-ATPase NTPDase2 and of nucleotide receptors by neuronal progenitor cells in the adult murine hippocampus. J Neurosci Res 80:600–610PubMedGoogle Scholar
  204. 204.
    Mishra SK, Braun N, Shukla V, Füllgrabe M, Schomerus C, Korf HW, Gachet C, Ikehara Y, Sévigny J, Robson SC, Zimmermann H (2006) Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation. Development 133:675–684PubMedGoogle Scholar
  205. 205.
    Milosevic J, Brandt A, Roemuss U, Arnold A, Wegner F, Schwarz SC, Storch A, Zimmermann H, Schwarz J (2006) Uracil nucleotides stimulate human neural precursor cell proliferation and dopaminergic differentiation: involvement of MEK/ERK signalling. J Neurochem 99:913–923PubMedGoogle Scholar
  206. 206.
    Rubini P, Milosevic J, Engelhardt J, Al-Khrasani M, Franke H, Heinrich A, Sperlagh B, Schwarz SC, Schwarz J, Nörenberg W, Illes P (2009) Increase of intracellular Ca2+ by adenine and uracil nucleotides in human midbrain-derived neuronal progenitor cells. Cell Cal 45:485–498Google Scholar
  207. 207.
    Lin JH, Takano T, Arcuino G, Wang X, Hu F, Darzynkiewicz Z, Nunes M, Goldman SA, Nedergaard M (2007) Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev Biol 302:356–366PubMedGoogle Scholar
  208. 208.
    Stafford MR, Bartlett PF, Adams DJ (2007) Purinergic receptor activation inhibits mitogen-stimulated proliferation in primary neurospheres from the adult mouse subventricular zone. Mol Cell Neurosci 35:535–548PubMedGoogle Scholar
  209. 209.
    Delarasse C, Gonnord P, Galante M, Auger R, Daniel H, Motta I, Kanellopoulos JM (2009) Neural progenitor cell death is induced by extracellular ATP via ligation of P2X7 receptor. J Neurochem 109:846–857PubMedGoogle Scholar
  210. 210.
    Wu PY, Lin YC, Chang CL, Lu HT, Chin CH, Hsu TT, Chu D, Sun SH (2009) Functional decreases in P2X7 receptors are associated with retinoic acid-induced neuronal differentiation of Neuro-2a neuroblastoma cells. Cell Signal 21:881–891PubMedGoogle Scholar
  211. 211.
    Grimm I, Ullsperger SN, Zimmermann H (2010) Nucleotides and epidermal growth factor induce parallel cytoskeletal rearrangements and migration in cultured adult murine neural stem cells. Acta Physiol (Oxf) 199:181–189Google Scholar
  212. 212.
    Khaira SK, Pouton CW, Haynes JM (2009) P2X2, P2X4 and P2Y1 receptors elevate intracellular Ca2+ in mouse embryonic stem cell-derived GABAergic neurons. Br J Pharmacol 158:1922–1931PubMedGoogle Scholar
  213. 213.
    Migita H, Kominami K, Higashida M, Maruyama R, Tuchida N, McDonald F, Shimada F, Sakurada K (2008) Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways. J Neurosci Res 86:2820–2828PubMedGoogle Scholar
  214. 214.
    Fedele DE, Koch P, Scheurer L, Simpson EM, Möhler H, Brüstle O, Boison D (2004) Engineering embryonic stem cell derived glia for adenosine delivery. Neurosci Lett 370:160–165PubMedGoogle Scholar
  215. 215.
    Guttinger M, Fedele D, Koch P, Padrun V, Pralong WF, Brüstle O, Boison D (2005) Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants. Epilepsia 46:1162–1169PubMedGoogle Scholar
  216. 216.
    Li T, Steinbeck JA, Lusardi T, Koch P, Lan JQ, Wilz A, Segschneider M, Simon RP, Brüstle O, Boison D (2007) Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants. Brain 130:1276–1288PubMedGoogle Scholar
  217. 217.
    Pignataro G, Studer FE, Wilz A, Simon RP, Boison D (2007) Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants. J Cereb Blood Flow Metab 27:919–927PubMedGoogle Scholar
  218. 218.
    Li J, Spletter ML, Johnson DA, Wright LS, Svendsen CN, Johnson JA (2005) Rotenone-induced caspase 9/3-independent and -dependent cell death in undifferentiated and differentiated human neural stem cells. J Neurochem 92:462–476PubMedGoogle Scholar
  219. 219.
    Riddle RC, Taylor AF, Rogers JR, Donahue HJ (2007) ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. J Bone Miner Res 22:589–600PubMedGoogle Scholar
  220. 220.
    Kawano S, Otsu K, Kuruma A, Shoji S, Yanagida E, Muto Y, Yoshikawa F, Hirayama Y, Mikoshiba K, Furuichi T (2006) ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells. Cell Cal 39:313–324Google Scholar
  221. 221.
    Coppi E, Pugliese AM, Urbani S, Melani A, Cerbai E, Mazzanti B, Bosi A, Saccardi R, Pedata F (2007) ATP modulates cell proliferation and elicits two different electrophysiological responses in human mesenchymal stem cells. Stem Cells 25:1840–1849PubMedGoogle Scholar
  222. 222.
    Ichikawa J, Gemba H (2009) Cell density-dependent changes in intracellular Ca2+ mobilization via the P2Y 2 receptor in rat bone marrow stromal cells. J Cell Physiol 219:372–381PubMedGoogle Scholar
  223. 223.
    Katebi M, Soleimani M, Cronstein BN (2009) Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development. J Leukoc Biol 85:438–444PubMedGoogle Scholar
  224. 224.
    Gharibi B, Elford C, Lewis BM, Ham J, Evans BAJ (2008) Evidence for adenosine receptor regulation of osteogenesis versus adipogenesis in mesenchymal stem cells. Calcif Tissue Int 83:9–10Google Scholar
  225. 225.
    Mohamadnejad M, Sohail MA, Watanabe A, Krause DS, Swenson ES, Mehal WZ (2010) Adenosine inhibits chemotaxis and induces hepatocyte-specific genes in bone marrow mesenchymal stem cells. Hepatology 51:963–973PubMedGoogle Scholar
  226. 226.
    Evans BA, Elford C, Pexa A, Francis K, Hughes AC, Deussen A, Ham J (2006) Human osteoblast precursors produce extracellular adenosine, which modulates their secretion of IL-6 and osteoprotegerin. J Bone Miner Res 21:228–236PubMedGoogle Scholar
  227. 227.
    Orciani M, Mariggiò MA, Morabito C, Di Benedetto G, Di Primio R (2010) Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol 23:124–132PubMedGoogle Scholar
  228. 228.
    Park KS, Kim YS, Kim JH, Choi BK, Kim SH, Oh SH, Ahn YR, Lee MS, Lee MK, Park JB, Kwon CH, Joh JW, Kim KW, Kim SJ (2009) Influence of human allogenic bone marrow and cord blood-derived mesenchymal stem cell secreting trophic factors on ATP (adenosine-5′-triphosphate)/ADP (adenosine-5′-diphosphate) ratio and insulin secretory function of isolated human islets from cadaveric donor. Transplant Proc 41:3813–3818PubMedGoogle Scholar
  229. 229.
    Scholze NJ, Zippel N, Müller CA, Pansky A, Tobiasch E (2009) P2X and P2Y receptors in human mesenchymal stem cell differentiation. Tiss Engineer Part A 15:698–699Google Scholar
  230. 230.
    Andrews EM, Tsai SY, Johnson SC, Farrer JR, Wagner JP, Kopen GC, Kartje GL (2008) Human adult bone marrow-derived somatic cell therapy results in functional recovery and axonal plasticity following stroke in the rat. Exp Neurol 211:588–592PubMedGoogle Scholar
  231. 231.
    Mahmood A, Lu D, Qu C, Goussev A, Chopp M (2005) Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats. Neurosurg 57:1026–1031Google Scholar
  232. 232.
    Boison D (2009) Engineered adenosine-releasing cells for epilepsy therapy: human mesenchymal stem cells and human embryonic stem cells. Neurotherapeut 6:278–283Google Scholar
  233. 233.
    Whetton AD, Huang SJ, Monk PN (1988) Adenosine triphosphate can maintain multipotent haemopoietic stem cells in the absence of interleukin 3 via a membrane permeabilization mechanism. Biochem Biophys Res Commun 152:1173–1178PubMedGoogle Scholar
  234. 234.
    Kalambakas SA, Robertson FM, O’Connell SM, Sinha S, Vishnupad K, Karp GI (1993) Adenosine diphosphate stimulation of cultured hematopoietic cell lines. Blood 81:2652–2657PubMedGoogle Scholar
  235. 235.
    Hatta Y, Aizawa S, Itoh T, Baba M, Horie T (1994) Cytotoxic effect of extracellular ATP on L1210 leukemic cells and normal hemopoietic stem cells. Leuk Res 18:637–641PubMedGoogle Scholar
  236. 236.
    Lemoli RM, Ferrari D, Fogli M, Rossi L, Pizzirani C, Forchap S, Chiozzi P, Vaselli D, Bertolini F, Foutz T, Aluigi M, Baccarani M, Di Virgilio F (2004) Extracellular nucleotides are potent stimulators of human hematopoietic stem cells in vitro and in vivo. Blood 104:1662–1670PubMedGoogle Scholar
  237. 237.
    Rossi L, Manfredini R, Bertolini F, Ferrari D, Fogli M, Zini R, Salati S, Salvestrini V, Gulinelli S, Adinolfi E, Ferrari S, Di Virgilio F, Baccarani M, Lemoli RM (2007) The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration. Blood 109:533–542PubMedGoogle Scholar
  238. 238.
    Yoon MJ, Lee HJ, Lee YS, Kim JH, Park JK, Chang WK, Shin HC, Kim DK (2007) Extracellular ATP is involved in the induction of apoptosis in murine hematopoietic cells. Biol Pharm Bull 30:671–676PubMedGoogle Scholar
  239. 239.
    Hofer M, Vacek A, Pospisil M, Weiterova L, Hola J, Streitova D, Znojil V (2006) Adenosine potentiates stimulatory effects on granulocyte-macrophage hematopoietic progenitor cells in vitro of IL-3 and SCF, but not those of G-CSF, GM-CSF and IL-11. Physiol Res 55:591–596PubMedGoogle Scholar
  240. 240.
    Hofer M, Pospisil M, Znojil V, Holá J, Streitová D, Vacek A (2008) Homeostatic action of adenosine A3 and A1 receptor agonists on proliferation of hematopoietic precursor cells. Exp Biol Med (Maywood) 233:897–900Google Scholar
  241. 241.
    Hofer M, Vacek A, Pospisil M, Hola J, Streitova D, Znojil V (2009) Activation of adenosine A3 receptors potentiates stimulatory effects of IL-3, SCF, and GM-CSF on mouse granulocyte-macrophage hematopoietic progenitor cells. Physiol Res 58:247–252PubMedGoogle Scholar
  242. 242.
    Lappas CM, Liu PC, Linden J, Kang EM, Malech HL (2010) Adenosine A2A receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation. J Leukoc Biol 87:345–354PubMedGoogle Scholar
  243. 243.
    Wurtman RJ, Cansev M, Sakamoto T, Ulus IH (2009) Use of phosphatide precursors to promote synaptogenesis. Annu Rev Nutr 29:59–87PubMedGoogle Scholar
  244. 244.
    Mamedova LK, Gao ZG, Jacobson KA (2006) Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors. Biochem Pharmacol 72:1031–1041PubMedGoogle Scholar
  245. 245.
    Rivkees SA, Zhao Z, Porter G, Turner C (2001) Influences of adenosine on the fetus and newborn. Mol Genet Metab 74:160–171PubMedGoogle Scholar
  246. 246.
    Tarnok A, Ulrich H (2001) Characterization of pressure-induced calcium response in neuronal cell lines. Cytometry 43:175–181PubMedGoogle Scholar
  247. 247.
    Martins AH, Resende RR, Majumder P, Faria M, Casarini DE, Tarnok A, Colli W, Pesquero JB, Ulrich H (2005) Neuronal differentiation of P19 embryonal carcinoma cells modulates kinin B2 receptor gene expression and function. J Biol Chem 280:19576–19586PubMedGoogle Scholar
  248. 248.
    Ulrich H, Majumder P (2006) Neurotransmitter receptor expression and activity during neuronal differentiation of embryonal carcinoma and stem cells: from basic research towards clinical applications. Cell Prolif 39:281–300PubMedGoogle Scholar

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Autonomic Neuroscience CentreUniversity College Medical SchoolLondonUK
  2. 2.Departamento de Bioquimica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil

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