Nucleotide Receptors Coupling to the Phospholipase C Signaling Pathway

  • Jean-Marie Boeynaems
  • Didier Communi
  • Rodolphe Janssens
  • Serge Motte
  • Bernard Robaye
  • Sabine Pirotton
Part of the The Receptors book series (REC)


The earliest papers reporting a stimulatory effect of extracellular nucleotides on inositol phosphate formation were published in 1985–1987 (Charest et al., 1985; Horstman et al., 1986; Pirotton et al., 1987; Forsberg et al., 1987). Since then the number of organs and cells in which nucleotides have been shown to produce an accumulation of inositol phosphates has been growing. A list which is not claimed to be exhaustive is provided in Table 1. These actions are mediated by at least two distinct receptors, P2Y and P2U, which have been identified according to the rank order of potency of various natural and synthetic agonists and on the basis of cross-desensitization experiments. Basically, the P2Y receptor is characterized by the high potency of 2-Methylthio ATP (2MeSATP) and related agonists (Burnstock et al., 1994), similar potencies of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) (the ratio being somewhat variable from one system to the other) and the lack of activity of UTP. It became apparent in the late eighties that, in many tissues and cells, not only ATP but also UTP is able to induce inositol phosphate formation. At that time it was proposed that the action of UTP is mediated by specific pyrimidinoceptors distinct from the purinoceptors (Seifert and Schultz, 1989). The existence of nucleotide or P2U receptors common to ATP and UTP constituted an alternative possibility, in favor of which experimental evidence started to accumulate: mainly the lack of additivity and the cross-desensitization of the responses to the two nucleotides (Brown et al., 1991; O’Connor et al., 1991; O’Connor, 1992).


Pertussis Toxin Inositol Phosphate Ehrlich Ascites Tumor Cell Extracellular Nucleotide RINm5F Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arkhammar, P., Hallberg, A., Kindmark, H., Nilsson, T., Rorsman, P., and Berggren, P. O. (1990) Extracellular ATP increases cytoplasmic free Ca2+ concentration in clonal insulin-producing RINm5F cells. Biochem. J. 265, 203–211.PubMedGoogle Scholar
  2. Ayyanathan, K., Webbs, T. E., Sandhu, A. K., Athwal, R. S., Barnard, E. A., and Kunapuli, S. P. (1996) Cloning and chromosomal localization of the human P2Y1 purinoceptor. Biochem. Biophys, Res. Commun. 218, 783–788.CrossRefGoogle Scholar
  3. Barnard, E. A., Burnstock, G., and Webb, T. E. (1994) G protein-coupled receptors for ATP and other nucleotides: a new receptor family. TIPS 15, 67–69.PubMedGoogle Scholar
  4. Berrie, C. P., Hawkins, P. T., Stephens, L. R., Harden, T. K., and Downes, C. P. (1988) Phosphatidylinositol 4, 5-bisphosphate hydrolysis in turkey erythrocytes is regulated by P2Y purinoceptors. Mol. Pharmacol. 35, 526–532.Google Scholar
  5. Berti-Mattera, L. N., Wilkins, P. L., Madhuin, Z., and Suchovsky, D. (1996) P2-purinergic receptors regulate phospholipase C and adenylate cyclase activities in immortalized Schwann cells. Biochem. J. 314, 555–561.PubMedGoogle Scholar
  6. Blachier, F. and Malaisse, W. J. (1988) Effect of exogenous ATP upon inositol phosphate production, cationic fluxes and insulin release in pancreatic islet cells. Biochim. Biophys. Acta 970, 222–229.PubMedCrossRefGoogle Scholar
  7. Boyer, J. L., Downes, C. P., and Harden, T. K. (1989) Kinetics of activation of phospholipase C by P2Y purinergic receptor agonists and guanine nucleotides. J. Biol. Chem. 264, 884–890.PubMedGoogle Scholar
  8. Brown, H. A., Lazarowski, E. R., Boucher, R. C., and Harden, T. K. (1991) Evidence that UTP and ATP regulate phospholipase C through a common extracellular 5′-nucleotide receptor in human airway epithelial cells. Mol. Pharmacol. 40, 648–655.PubMedGoogle Scholar
  9. Burnstock, G., Fischer, B., Hoyle, C. H. V., Maillard, M., Ziganshin, A. U., Brizzolara, A. L., Von Isakovics, A., Boyer, J. L., Harden T. K., and Jacobson K. A. (1994) Structure activity relationships for derivatives of adenosine-5′-triphosphate as agonists at P2 purinoceptors: heterogeneity within P2x and P2Y subtypes. Drug Dev. Res. 31, 206–219.PubMedCrossRefGoogle Scholar
  10. Chang, K., Hanaoka, K., Kumada, M., and Takuwa, Y. (1995) Molecular cloning and functional analysis of a novel P2 nucleotide receptor. J. Biol. Chem. 270, 26, 152–226, 158.Google Scholar
  11. Charest, R., Blackmore P. F., and Exton, J. H. (1985) Characterization of responses of isolated rat hepatocytes to ATP and ADP. J. Biol. Chem. 260, 15, 789–815, 794.Google Scholar
  12. Communi, D., Raspe, E., Pirotton, S., and Boeynaems, J-M. (1995a) Coexpression of P2Y and P2u receptors on aortic endothelial cells. Circ. Res. 76, 191–198.PubMedCrossRefGoogle Scholar
  13. Communi, D., Pirotton, S., Parmentier, M., and Boeynaems, J-M. (1995b) Cloning and functional expression of a human uridine nucleotide receptor. J. Biol. Chem. 270, 30, 849–930, 852.Google Scholar
  14. Communi, D., Parmentier, M., and Boeynaems, J-M. (1996a) Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem. Biophys. Res. Commun. 222, 303–308.PubMedCrossRefGoogle Scholar
  15. Communi, D., Motte, S., Boeynaems, J-M., Pirotton, S. (1996b) Pharmacological characterization of the human P2Y4 receptor. Eur. J. Pharmacol. 317, 383–389.PubMedCrossRefGoogle Scholar
  16. Daniel, J. L., Dangelmaier, C. A., Selak, M., and Smith, J. B. (1986) ADP stimulates IP3 formation in human platelets. FEBS Lett. 206, 299–303.PubMedCrossRefGoogle Scholar
  17. Davidson, J. S., Wakefield, I. K., Sohnius, U., Van Der Merwe, P. A., and Millar, R. P. (1990) A novel extracellular nucleotide receptor coupled to phosphoinositi-dase-C in pituitary cells. Endocrinology 126, 80–87.PubMedCrossRefGoogle Scholar
  18. Dubyak, G. R., Cowen, D. S., and Meuller, L. M. (1988) Activation of inositol phospholipid breakdown in HL60 cells by P2-purinergic receptors for extracellular ATP. J. Biol. Chem. 263, 18, 108–218, 117.Google Scholar
  19. Dubyak, G.R. (1986) Extracellular ATP activates polyphosphoinositide breakdown and Ca2+ mobilization in Ehrlich ascites tumor cells. Arch. Biochem. Biophys. 245, 84–95.PubMedCrossRefGoogle Scholar
  20. Erlinge, D., You, J., Wahlestedt, C., and Edvinsson, L. (1995) Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells. Eur. J. Pharmacol. 289, 135–149.PubMedCrossRefGoogle Scholar
  21. Fang, W-G., Pirnia, F., Bang, Y-J., Myers, C. E., and Trepel, J. B. (1992) P2-purinergic receptor agonists inhibit the growth of androgen-independent prostate carcinoma cells. J. Clin. Invest. 89, 191–196.PubMedCrossRefGoogle Scholar
  22. Filippini, A., Riccioli, A., De Cesaris, P., Paniccia, R., Teti, A., Stefanini, M., Conti, M., and Ziparo, E. (1994) Activation of inositol phospholipid turnover and calcium signaling in rat Sertoli cells by P2-purinergic receptors: modulation of Follicle-Stimulating Hormone responses. Endocrinology 134, 1537–1545.PubMedCrossRefGoogle Scholar
  23. Filtz, T. M., Li, Q., Boyer, J. L., Nicholas, R. A., and Harden, T. K. (1994) Expression of a cloned P2Y purinergic receptor that couples to phospholipase C. Mol. Pharmacol. 46, 8–14.PubMedGoogle Scholar
  24. Fine, J., Cole, P., and Davidson, J. S. (1989) Extracellular nucleotides stimulate receptor-mediated calcium mobilization and inositol phosphate production in human fibroblasts. Biochem. J. 263, 371–376.PubMedGoogle Scholar
  25. Fisher, G. J., Bakshian, S., and Baldassare, J. J. (1985) Activation of human platelets by ADP causes a rapid rise in cytosolic free calcium without hydrolysis of phosphati-dylinositol-4, 5-bisphosphate. Biochem. Biophys. Res. Commun. 129, 958–964.PubMedCrossRefGoogle Scholar
  26. Forsberg, E. J., Feuerstein, G., Shohami, E., and Pollard, H. B. (1987) Adenosine tri-phosphate stimulates inositol phospholipid metabolism and prostacyclin formation in adrenal medullary endothelial cells by means of P2-purinergic receptors. Proc. Natl. Acad. Sci USA 84, 5630–5634.PubMedCrossRefGoogle Scholar
  27. Fredholm, B. B., Abbracchio, M. P., Burnstock, G., Daly, J. W., Harden, T. K., Jacobson, K. A., Leff, P., and Williams, M. (1994) VI. Nomenclature and Classification of Purinoceptors. Pharmacol. Rev. 46, 143–153.PubMedGoogle Scholar
  28. Frelin, C., Breittmayer, J. P., and Vigne, P. (1993) ADP induces inositol phosphate-independent intracellular Ca2+ mobilization in brain capillary endothelial cells. J. Biol. Chem. 268, 8787–8792.PubMedGoogle Scholar
  29. Gallinaro, B. J., Reimer, W. J., and Dixon, S. J. (1995) Activation of protein kinase C inhibits ATP-induced [Ca2+] elevation in rat osteoblastic cells: selective effects on P2Y and P2U signaling pathways. J. Cell. Physiol. 162, 305–314.PubMedCrossRefGoogle Scholar
  30. Gerwins, P. and Fredholm, B. B. (1992) ATP and its metabolite adenosine act syner-gistically to mobilize intracellular calcium via the formation of inositol 1,4,5-tris-phosphate in a smooth muscle cell line. J. Biol. Chem. 267, 16, 081–116, 087.Google Scholar
  31. Gonzalez, F. A., Alfonzo, R. G., Toro, J. R., and Heppel, L. A. (1989a) Receptor specific for certain nucleotides stimulates inositol phosphate metabolism and Ca2+ fluxes in A431 cells. J. Cell Physiol. 141, 606–617.PubMedCrossRefGoogle Scholar
  32. Gonzalez, F. A., Rozengurt, E., and Heppel, L. A. (1989b) Extracellular ATP induces the release of calcium from intracellular stores without the activation of protein kinase C in Swiss 3T6 mouse fibroblasts. Proc. Natl Acad. Sci. USA 86, 4530–4534.PubMedCrossRefGoogle Scholar
  33. Griese, M., Gobran, L. I., and Rooney, S. A. (1991) ATP-stimulated inositol phospholipid metabolism and surfactant secretion in rat type II pneumocytes. Am. J. Physiol. 260, L586–L593.PubMedGoogle Scholar
  34. Heemskerk, J. W. M., Vis, P., Feijge, M. A. H., Hoyland, J., Mason, W. T., and Sage, S. O. (1993) Roles of phospholipase C and Ca2+-ATPase in calcium responses of single fibrinogen-bound platelets. J. Biol. Chem. 268, 356–363.PubMedGoogle Scholar
  35. Henderson, D. J., Elliot, D. G., Smith, G. M., Webb, T. E., and Dainty, I. A. (1995) Cloning and characterisation of a bovine P2Y receptor. Biochem. Biophys. Res. Commun. 212, 648–656.PubMedCrossRefGoogle Scholar
  36. Henning, R. H., Duin, M., Den Hertog, A., and 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, 747–752.PubMedCrossRefGoogle Scholar
  37. Hoiting, B., Molleman, A., Nelemans, A., and Den Hertog, A. (1990) P2-purinoceptor-activated membrane currents and inositol tetrakisphosphate formation are blocked by suramin. Eur. J. Pharmacol. 181, 127–131.PubMedCrossRefGoogle Scholar
  38. Hoey, E. D., Nicol, M., Williams, B. C., and Walker, S. W. (1994) Primary cultures of bovine inner zone adrenocortical cells secrete cortisol in response to adenosine triphosphate, adenosine diphosphate, and undine triphosphate via a nucleotide receptor which may be coupled to two signal generation systems. Endocrinology 134, 1553–1560.PubMedCrossRefGoogle Scholar
  39. Horstman, D. A., Tennes, K. A., and Putney, J. W. Jr. (1986) ATP-induced calcium mobilization and inositol 1,4,5-trisphosphate formation in H-35 hepatoma cells. FEBS Lett. 204, 189–192.PubMedCrossRefGoogle Scholar
  40. Hourani, S. M. O. and Hall, D. A. (1994) Receptors for ADP on human blood platelets. TIPS 15, 103–108.PubMedGoogle Scholar
  41. Iredale, P. A. and Hill, S. J. (1993) Increases in intracellular calcium via activation of an endogenous P2-purinoceptor in cultured CHO-K1 cells. Br. J. Pharmacol. 110, 1305–1310.PubMedCrossRefGoogle Scholar
  42. Janssens, R., Communi, D., Pirotton, S., Samson, M., Parmentier, M., and Boeynaems, J-M. (1996) Cloning and tissue distribution of the human P2Y1 receptor. Biochem. Biophys. Res. Commun. 221, 588–593.PubMedCrossRefGoogle Scholar
  43. Jorgensen, T. D., Gromada, J., Tritsaris, K., Nauntofte, B., and Dissing, S. (1995) Activation of P2z purinoceptors diminishes the muscarinic cholinergicinduced release of inositol 1,4,5-triphosphate and stored calcium in rat parotid acini. Biochem. J. 312, 457–464.PubMedGoogle Scholar
  44. Keppens, S. and De Wulf, H. (1995) Some P2 purinergic agonists increase cytosolic calcium but not inositol 1,4,5-trisphosphate in isolated rat hepatocytes. Biochim. Biophys. Acta 1269, 316–322.PubMedCrossRefGoogle Scholar
  45. Kumagai, M., Sacktor, B., and Filburn, C. R. (1991) Purinergic regulation of cytosolic calcium and phosphoinositide metabolism in rat osteoblast-like osteosarcoma cells. J. Bone. Miner. Res. 6, 697–708.PubMedCrossRefGoogle Scholar
  46. Lazarowski, E. R., Boucher, R. C., and Harden, T. K. (1994) Calcium-dependent release of arachidonic acid in response to purinergic receptor activation in airway epithelium. Am. J. Physiol. 266, C406–C415.PubMedGoogle Scholar
  47. Lazarowski, E. R. and Harden, T. K. (1994) Identification of a uridine nucleotide-selective G-protein-linked receptor that activates phospholipase C. J. Biol. Chem. 269, 11, 830–911, 836.Google Scholar
  48. Lazarowski, E. R., Watt, W. C., Stutts, M. J., Boucher, R. C., and Harden, T. K. (1995) Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate. Br. J. Pharmacol. 116, 1619–1627.PubMedCrossRefGoogle Scholar
  49. Legssyer, A., Poggioli, J., Renard, D., and Vassort, G. (1988) ATP and other adenine compounds increase mechanical activity and inositol trisphosphate production in rat heart. J. Physiol. 401, 183–199.Google Scholar
  50. Li, G., Milani, D., Dunne, M. J., Pralong, W. F., Théier, J-M., Peterson, O. H., and Wollheim, C. B. (1991) Extracellular ATP causes Ca2+-dependent and independent insulin secretion in RINm5F cells. J. Biol. Chem. 266, 3449–3457.PubMedGoogle Scholar
  51. Lin, T-A., Lustig, K. D., Sportiello, M. G., Weisman, G. A., and Sun, G. Y. (1993) Signal transduction pathways coupled to a P2U receptor in neuroblastoma X glioma (NG108-15) cells. J. Neurochem. 60, 1115–1125.PubMedCrossRefGoogle Scholar
  52. Lin, W-W. and Chuang, D-M. (1994) Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 gioma cells. J. Pharmacol. Exp. Ther. 269, 926–933.PubMedGoogle Scholar
  53. Liu, J., Conklin, B. R., Blin, N., Yun, J., and Wess, J. (1995) Identification of a receptor/G-protein contact site critical for signaling specificity and G-protein activation. Proc. Natl. Acad. Sci. USA 92, 11, 642–711, 646.CrossRefGoogle Scholar
  54. Lustig, K. D., Erb, L., Landis, D. M., Hicks-Taylor, C. S., Zhang, X., Sportiello, M. G., and Weisman, G. A. (1992) Mechanisms by which extracellular ATP and UTP stimulate the release of prostacyclin from bovine pulmonary artery endothelial cells. Biochim. Biophys. Acta 1134, 61–72.PubMedCrossRefGoogle Scholar
  55. Lustig, K. D., Shiau, A. K., Brake, A. J., and Julius, D. (1993) Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc. Natl. Acad. Sci. USA 90, 5113–5117.PubMedCrossRefGoogle Scholar
  56. Mannix, R. J., Moatter, T., Kelley, K. A., and Gerritsen, M. E. (1993) Cellular signaling responses mediated by a novel nucleotide receptor in rabbit microvessel endothelium. Am. J. Physiol. 34, H675–H680.Google Scholar
  57. Martin, M. W. and Harden, T. K. (1989) Agonist-induced desensitization of a P2Y-purinergic receptor regulated phospholipase C. J. Biol. Chem. 264, 19, 535–619, 539.Google Scholar
  58. Maurice, D. H., Waldo, G. L., Morris, A. J., Nicholas, R. A., and Harden, T. K. (1993) Identification of G alpha 11 as the phospholipase C-activating G-protein of turkey erythrocytes. Biochem. J. 290, 765–770.PubMedGoogle Scholar
  59. Morris, A. J., Waldo, G. L., Downes, C. P., and Harden, T. K. (1990a) A receptor and G-protein-regulated polyphosphoinositide-specific phospholipase C from turkey erythrocytes (I). J. Biol. Chem. 265, 13, 501–613, 507.Google Scholar
  60. Morris, A. J., Waldo, G. L., Downes, C. P., and Harden, T. K. (1990b) A receptor and G-protein-regulated polyphosphoinositide-specific phospholipase C from turkey erythrocytes (II). J. Biol. Chem. 265, 13, 508–613, 514.Google Scholar
  61. Motte, S., Pirotton, S., and Boeynaems, J-M. (1993) Heterogeneity of ATP receptors in aortic endothelial cells Involvement of P2Y and P2U receptors in the inositol phosphate response. Circ. Res. 72, 504–510.PubMedCrossRefGoogle Scholar
  62. Murrin, R. J. A. and Boarder, M. R. (1991) Neuronal nucleotide receptor linked to phospholipase C and phospholipase D Stimulation of PC12 cells by ATP analogues and UTP. Mol. Pharmacol. 41, 561–568.Google Scholar
  63. Nanoff, C., Freissmuth, M., Tuisl, E., and Schutz, W. (1990) P2-, but not P1-purinoceptors, mediate formation of 1,4,5-inositol trisphosphate and its metabolites via a pertussis toxin-insensitive pathway in the rat renal cortex. Br. J. Pharmacol. 100, 63–68.PubMedCrossRefGoogle Scholar
  64. Nguyen, T., Erb, L., Weisman, G. A., Marchese, A., Heng, H. H. Q, Garrad, R. C., George, S. R., Turner, J.T., and O’Dowd, B. F. (1995) Cloning, expression and chromosomal localization of the human uridine nucleotide receptor gene. J. Biol. Chem. 270, 30, 845–930, 848.Google Scholar
  65. O’Connor, S. E. (1992) Recent developments in the classification and functional significance of receptors for ATP and UTP: evidence for nucleotide receptors. Life Sci. 50, 1657–1664.CrossRefGoogle Scholar
  66. O’Connor, S. E., Dainty, I. A., and Leff, P. (1991) Further subclassification of ATP receptors based on agonist studies. TIPS 12, 137–141.Google Scholar
  67. Ohlmann, P., Laugwitz, K-L., Nürnberg, B., Spicher, K., Schultz, G., Cazenave, J-P., and Gachet, C. (1995) The human platelet ADP receptor activates G12 proteins. Biochem. J. 312, 775–779.PubMedGoogle Scholar
  68. Okajima, F., Sato, K., Nazarea, M., Sho, K., and Kondo, Y. (1988) A permissive role of pertussis toxin substrate G-protein in P2-purinergic stimulation of phosphoinositide turnover and arachidonate release in FRTL-5 thyroid cells. J. Biol. Chem. 264, 13, 029–113, 037.Google Scholar
  69. Okajima, F., Sato, K., and Kondo Y. (1989) P2-purinergic agonists activate phospholipase C in a guanine nucleotide-and Ca2+-dependent manner in FRTL-5 thyroid cell membranes. FEBS Lett. 253, 132–136.PubMedCrossRefGoogle Scholar
  70. Olbrich, C., Aepfelbacher, M., and Siess, W. (1989) Epinephrine potentiates calcium mobilization and activation of protein kinases in platelets stimulated by ADP through a mechanism unrelated to phospholipase C. Cell. Signal. 1, 483–492.PubMedCrossRefGoogle Scholar
  71. Packham, M. A., Livne, A-A., Ruben, D. H., and Rand, M. L. (1993) Activation of phospholipase C and protein kinase C has little involvement in ADP-induced primary aggregation of human platelets: effects of diacylglycerols, the diacylglycerol kinase inhibitor R59022, staurosporine and okadaic acid. Biochem. J. 290, 849–856.PubMedGoogle Scholar
  72. Parr, C. E., Sullivan, D. M., Paradiso, A. M., Lazarowski, E. R., Burch, L. H., Olsen, J. C., Erb, L., Weisman, G. A., Boucher, R. C., and Turner, J. T. (1994) Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. Proc. Natl. Acad. Sci. USA 91, 3275–3279.PubMedCrossRefGoogle Scholar
  73. Paulmichl, M., Pfeilschifter, J., Woll, E., and Lang, F. (1991) Cellular mechanisms of ATP-induced hyperpolarization in renal epitheloid MDCK-cells. J. Cell. Physiol. 147, 68–75.PubMedCrossRefGoogle Scholar
  74. Pearce, B., Murphy, S., Jeremy, J., Morrow, C., and Dandona, P. (1989) ATP-evoked Ca2+ mobilisation and prostanoid release from astrocytes: P2-purinergic receptors linked to phosphoinositide hydrolysis. J. Neurochem. 52, 971–977.PubMedCrossRefGoogle Scholar
  75. Pfeilschifter, J., Thüring, B., and Festa, F. (1989) Extracellular ATP stimulates poly (inositol phospholipid) hydrolysis and eicosanoid synthesis in mouse peritoneal macrophages in culture. Eur. J. Biochem. 186, 509–513.PubMedCrossRefGoogle Scholar
  76. Pfeilschifter, J. (1990) Comparison of extracellular ATP and UTP signalling in rat renal mesangial cells. Biochem. J. 272, 469–472.PubMedGoogle Scholar
  77. Phaneuf, S., Berta, P., Casanova, J., and Cavadore, J-C. (1987) ATP stimulates inositol phosphates accumulation and calcium mobilization in a primary culture of rat aortic myocytes. Biochem. Biophys. Res. Commun. 143, 454–460.PubMedCrossRefGoogle Scholar
  78. Pillai, S. and Bikle, D. D. (1992) Adenosine triphosphate stimulates phosphoinositide metabolism, mobilizes intracellular calcium, and inhibits terminal differentiation of human epidermal keratinocytes. J. Clin Invest. 90, 42–51.PubMedCrossRefGoogle Scholar
  79. Pirotton, S., Raspe, E., Demolie, D., Erneux, C., and Boeynaems, J-M. (1987) Involvement of inositol 1,4,5-trisphosphate in the action of adenine nucleotides on aortic endothelial cells. J. Biol. Chem. 262, 17, 461–517, 466.Google Scholar
  80. Purkiss, J. R., Wilkinson, G. F., and Boarder, M. R. (1993) Evidence for a nucleotide receptor on adrenal medullary endothelial cells linked to phospholipase C and phospholipase D. Br. J. Pharmacol. 108, 1031–1037.PubMedCrossRefGoogle Scholar
  81. Raha, S., De Souza, L. R., and Reed, J. K. (1993) Intracellular signalling by nucleotide receptors in PC12 pheochromocytoma cells. J. Cell. Physiol. 154, 623–630.PubMedCrossRefGoogle Scholar
  82. Reimer, W. J. and Dixon, S. J. (1992) Extracellular nucleotides elevate [Ca2+]i in rat osteoblastic cells by interaction with two receptor subtypes. Am. J. Physiol. 263, C1040–C1048.PubMedGoogle Scholar
  83. Rice, W. R., Burton, F. M., and Fiedeldey, D. T. (1995) Cloning and expression of the alveolar type II cell P2U-purinergic receptor. Am. J. Respir. Cell. Mol. Biol. 12, 27–32.PubMedGoogle Scholar
  84. Sasakawa, N., Nakaki, T., Yamamoto, S., and Kato, R. (1989) Stimulation by ATP of inositol trisphosphate accumulation and calcium mobilization in cultured adrenal chromaffin cells. J. Neurochem. 52, 441–447.PubMedCrossRefGoogle Scholar
  85. Schöfl, C., Rössig, L., Potter, E., Von Zur Mühlen, A., and Brabant, G. (1995) Extracellular ATP and UTP increase cytosolic free calcium by activating a common P2U-receptor in single human thyrocytes. Biochem. Biophys. Res. Commun. 213, 928–934.PubMedCrossRefGoogle Scholar
  86. Seifert, R. and Schultz, G. (1989) Involvement of pyrimidinoceptors in the regulation of cell functions by uridine and by uracil nucleotides. TIPS 10, 365–369.PubMedGoogle Scholar
  87. Simon, J., Webb, T. E., King, B. F., Burnstock, G., and Barnard, E. A. (1995) Characterisation of a recombinant P2Y purinoceptor. Eur. J. Pharmacol. 291, 281–289.PubMedCrossRefGoogle Scholar
  88. Stubbs, E. B. Jr, Walker, B. A. M., Owens, C. A., Ward, P. A., and Agranoff, B. W. (1992) Formyl peptide stimulates and ATPγS potentiates [3H] cytidine 5′-diphos-phate diglyceride accumulation in human neutrophils. J. Immunol. 148, 2242–2247.PubMedGoogle Scholar
  89. Stutchfield, J. and Cockcroft, S. (1990) Undifferentiated HL60 cells respond to extracellular ATP and UTP by stimulating phospholipase C activation and exocytosis. FEBS Lett. 262, 256–258.PubMedCrossRefGoogle Scholar
  90. Takemura, S., Kawada, N., Hirohashi, K., Kinoshita, H., and Inoue, M. (1994) Nucleotide receptors in hepatic stellate cells of the rat. FEBS Lett. 354, 53–56.PubMedCrossRefGoogle Scholar
  91. Tokuyama, Y., Hara, M., Jones, E. M. C., Fan, Z., and Bell, G. J. (1995) Cloning of rat and mouse P2Y purinoceptors. Biochem. Biophys. Res. Commun. 211, 211–218.PubMedCrossRefGoogle Scholar
  92. Vander Kooy, D., Dubyak, G. R., Moore, R. M., and Moore J. J. (1989) Adenosine triphosphate activates the phospholipase-C cascade system in human amnion cells without increasing prostaglandin production. Endocrinology 124, 2005–2012.CrossRefGoogle Scholar
  93. Vickers, J. D., Kinlough-Rathbone, R. L., Packham, M. A., and Mustard, J. F. (1990) Inositol phospholipid metabolism in human platelets stimulated by ADP. Eur. J. Biochem. 193, 521–528.PubMedCrossRefGoogle Scholar
  94. Waldo, G. L., Boyer, J. L., Morris, A. J., and Harden, T. K. (1991) Purification of an A1F4- and G-protein beta gamma-subunit-regulated phospholipase C-activating protein. J. Biol. Chem. 266, 14, 217–314, 225.Google Scholar
  95. Webb, T. E., Simon, J., Krishek, B. J., Bateson, A. N., Smart, T. G., King, B. F., Burnstock, G., and Barnard, E. A. (1993) Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett. 324, 219–225.PubMedCrossRefGoogle Scholar
  96. Webb, T. E., Kaplan, M. G., and Barnard, E. A. (1996a) Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem. Biophys. Res. Commun. 219, 105–110.PubMedCrossRefGoogle Scholar
  97. Webb, T. E., Henderson, D., King, B. F., Wang, S. Y., Simon, J., Bateson, A. N., Burnstock, G. and Barnard, E. A. (1996b) A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially by nucleoside diphosphates. Mol. Pharmacol. 50, 258–265.PubMedGoogle Scholar
  98. Wilkinson, G. F., Purkiss, J. R., and Boarder, M. R. (1993) The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing P2Y-purinoceptors and nucleotide receptors linked to phospholipase C. Br. J. Pharmacol. 108, 689–693.PubMedCrossRefGoogle Scholar
  99. Yu, H. and Turner, J. T. (1991) Functional studies in the human submandibular duct cell line, HSG-PA, suggest a second salivary gland receptor subtype for nucleotides. J. Pharmacol. Exp. Therap. 259, 1344–1350.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Jean-Marie Boeynaems
  • Didier Communi
  • Rodolphe Janssens
  • Serge Motte
  • Bernard Robaye
  • Sabine Pirotton

There are no affiliations available

Personalised recommendations