P1 and P2 Purine and Pyrimidine Receptor Ligands

  • K. A. Jacobson
  • L. J. S. Knutsen
Chapter
Part of the Purinergic and Pyrimidinergic Signalling book series (HEP, volume 151 / 1)

Abstract

Research focused on P1 and P2 purinergic receptor function is currently at a critical stage where considerable efforts in the disciplines of medicinal chemistry, molecular biology, and pharmacology have resulted in the identification of a number of novel ligands that have been used to enhance understanding of the roles of both P1 (adenosine) and P2 (ATP, ADP, UTP and UDP) receptors in human tissue function.

Keywords

Pyrimidine Phosphonate Ribose Carbachol Dihydropyridine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbracchio MP, Burnstock G (1998) Purinergic signalling: pathophysiological roles. Jap J Pharmacol 78: 113–145PubMedGoogle Scholar
  2. Abbracchio MP, Rainaldi G, Giammarioli AM, Ceruti S, Brambilla R, Cattabeni F, Barbieri D, Franceschi C, Jacobson KA, Malorni W (1997) The A3 adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bc1-xL: studies in human astroglioma cells. Biochem Biophys Res Commun 241: 297–304PubMedGoogle Scholar
  3. Adami M, Bertorelli R, Ferri N, Foddi MC, Ongini E (1995) Effects of repeated administration of selective adenosine AI and A2A receptor agonists on pentylenetetrazole-induced convulsions in the rat. Eur J Pharmacol 294: 383–389PubMedGoogle Scholar
  4. Alberti C, Monopoli A, Casati C, Forlani A, Sala C, Nador B, Ongini E, Morganti A (1997) Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists. J Cardiovasc Pharmacol 30: 320–324PubMedGoogle Scholar
  5. Ali H, Choi OH, Fraundorfer PF, Yamada K, Gonzaga HMS, Beaven MA (1996) Sustained activation of phospholipase D via adenosine A3 receptors is associated with enhancement of antigen-and Ca’-ionophore-induced secretion in a rat mast cell line. J Pharmacol Exp Ther 276: 837–845PubMedGoogle Scholar
  6. Allgaier C, Wellmann H, Schobert A, von Kuegelgen I (1995) Cultured chick sympathetic neurons: modulation of electrically evoked noradrenaline release by P2purinoceptors. Naunyn-Schmiedebergs Arch Pharmacol 352: 17–24PubMedGoogle Scholar
  7. Arispe N, Ma J, Jacobson KA, Pollard HB (1998) Direct activation of cystic fibrosis transmembrane conductance regulator channels by 8-cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylxanthine ( DAX ). J Biol Chem 273: 5727–5734Google Scholar
  8. Auchampach JA, Rizvi A, Qiu Y, Tang X-L, Maldonado C, Teschner S, Bolli R (1997) Selective activation of A3 adenosine receptors with N6-(3-iodobenzyl)adenosine5’-N-methyluronamide protects against myocardial stunning and infarction without hemodynamic changes in conscious rabbits. Circ Res 80: 800–809PubMedGoogle Scholar
  9. Baraldi PG, Cacciari B, Spalluto G, Pineda de Villatoro MJ, Zocchi C, Dionisotti S, Ongini E (1996) Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives: Potent and Selective A2A Adenosine Antagonists. J Med Chem 39: 1164–1171PubMedGoogle Scholar
  10. Baraldi PG, Manfredini S, Simoni D, Zappaterra L, Zocchi C, Dionisotti S, Ongini E (1994) Synthesis of new pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and 1,2,3triazolo[4,5-e]1,2,4-triazolo[1,5-c]pyrimidine displaying potent and selective activity as A2A adenosine receptor antagonists. Bioorg Med Chem Lett 4: 2539–2544Google Scholar
  11. Barraco RA, Aggarwal AK, Phillis JW, Moron MA, Wu PH (1984) Dissociation of the locomotor and hypotensive effects of adenosine analogs in the rat. Neurosci Lett 48: 139–144PubMedGoogle Scholar
  12. Barraco RA, Martens KA, Parizon M, Normile HJ (1994) Role of adenosine A2A receptors in the nucleus accumbens. Prog Neuro-Psychopharmacol Biol Psychiatry 18: 545–553Google Scholar
  13. Belardinelli L, Lu J, Dennis D, Martens J, Shryock JC (1994) The cardiac effects of a novel A1-adenosine receptor agonist in guinea pig isolated heart. J Pharmacol Exp Ther 271: 1371–1382PubMedGoogle Scholar
  14. Bertolet BD, Anand IS, Bryg RJ, Mohanty PK, Chatterjee K, Cohn JN, Khurmi NS, Pepine CJ (1996) Effects of A, adenosine receptor agonism using N6-cyclohexyl2’-O-methyladenosine in patients with left ventricular dysfunction. Circulation 94: 1212–1215PubMedGoogle Scholar
  15. Bertorelli R, Ferri N,Adami M, Ongini E (1996) Effects of selective agonists and antagonists for A, or A2A adenosine receptors on sleep-waking patterns in rats Drug Dev Res 37: 65–72Google Scholar
  16. Beukers MW, Kerkhof CJM, van Rhee MA, Ardanuy U, Gurgel C, Widjaja H, Nickel P, IJzerman AP, Soudijn W (1995) Suramin analogs, divalent cations and ATP1S as inhibitors of ecto-ATPase. Naunyn-Schmiedebergs Arch Pharmacol 351: 523528Google Scholar
  17. Bhagwat SS, Williams M (1997). P2 Purine and pyrimidine receptors: emerging super-families of G-protein coupled and ligand gated ion channel receptors. Eur J Med Chem 32: 183–193Google Scholar
  18. Bianchi BR, Lynch KJ, Touma E, Niforatos W, Burgard EC, Alexander KM, Park HS, Yu H, Metzger R, Kowaluk E, Jarvis M, van Biesen T (1999) Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur J Pharmacol 376: 127–138PubMedGoogle Scholar
  19. Bona E, Aden U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists. Neuropharmacology 36: 1327–1338PubMedGoogle Scholar
  20. Boyer JL, Zohn IE, Jacobson KA, Harden TK (1994) Differential effects of P2purinoceptor antagonists on phospholipase C- and adenylyl cyclase-coupled P2Ypurinoceptors. Br J Pharmacol 113: 614–620PubMedGoogle Scholar
  21. Boyer JL, Siddiqi S, Fischer B, Romera-Avila T, Jacobson KA, Harden TK (1996) Identification of potent P2Y purinoceptor agonists that are derivatives of adenosine 5’-monophosphate. Br J Pharmacol 118: 1959–1964PubMedGoogle Scholar
  22. Boyer JL, Mohanram A, Camaioni E, Jacobson KA, Harden TK (1998) Competitive and selective antagonism of P2Y, receptors by N6-methyl 2’-deoxyadenosine 3’,5’bisphosphate. Brit J Pharmacol 124: 1–3Google Scholar
  23. Bruns RF, Fergus JH, Badger EW, Bristol JA, Santay LA, Hartman JD, Hays SJ, Huang, CC (1987) Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3dipropylxanthine to rat brain membranes. Naunyn-Schmiedebergs Arch Pharmacol 335: 59–63PubMedGoogle Scholar
  24. Bruns RF, Lu GH, Pugsley TA (1986) Characterization of the A2 adenosine receptor labelled by [3H]NECA in rat striatal membranes. Mol Pharmacol 29: 331–346PubMedGoogle Scholar
  25. Bueltmann R, Wittenburg H, Pause B, Kurz G, Nickel P, Starke K (1996) P2purinoceptor antagonists. Part 3. Blockade of P2-purinoceptor subtypes and ecto-nucleotidases by compounds related to suramin. Naunyn-Schmiedebergs Arch Pharmacol 354: 498–504Google Scholar
  26. Burnstock G, Warland JJ (1987) P2-purinoceptors of two subtypes in the rabbit mesenteric artery: Reactive Blue 2 selectively inhibits responses mediated via the P2Ybut not the P2X-purinoceptor. Brit J Pharmacol 90: 383–391Google Scholar
  27. Burnstock G, Fischer B, Hoyle CHV, Maillard M, Ziganshin AU, Brizzolara AL, von Isakovics A, Boyer JL, Harden TK, Jacobson KA (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: 206–219PubMedGoogle Scholar
  28. Camaioni E, Boyer JL, Mohanram A, Harden TK, Jacobson KA (1998) Deoxyadenosine-bisphosphate derivatives as potent antagonists at P2Y, receptors. J Med Chem 41: 183–190PubMedGoogle Scholar
  29. Casati C, Monopoli A, Dionisotti S, Zocchi C, Bonizzoni E, Ongini E (1994) Repeated administration of selective adenosine AI and A2 receptor agonists in the spontaneously hypertensive rat: tolerance develops to A,-mediated hemodynamic effects. J Pharmacol Exp Ther 268: 1506–1511PubMedGoogle Scholar
  30. Charlton S, Brown CA, Boarder MR (1996) Suramin and PPADS antagonists at transfected P2Y1, P2Y2, P2Y, and P2Y4 receptors. Drug Dev Res 37: 113Google Scholar
  31. Chesi AJR, Stone TW (1997) Alkylxanthine adenosine antagonists and epileptiform activity in rat hippocampal slices in vitro. Exp Brain Res 113: 303–310PubMedGoogle Scholar
  32. Chessell IP, Simon J, Hibell AD, Michel AD, Barnard EA, Humphrey PPA (1998) Cloning and functional characterization of the mouse P2X7 receptor. FEBS Lett 439: 26–30PubMedGoogle Scholar
  33. Coffin VL, Spealman RD (1987) Behavioral and cardiovascular effects of analogs of adenosine in cynomolgus monkeys. J Pharmacol Exp Ther 241: 76–83PubMedGoogle Scholar
  34. Communi O, Boeynaems JM (1997) Receptors responsive to extracellular pyrimidine nucleotides. Trends Pharmacol Sci 18:83 —86Google Scholar
  35. Conant AR, Fisher MJ, McLennan AG, Simpson AWM (1998) Characterization of the P2 receptors on the human umbilical vein endothelial cell line ECV304. Br J Pharmacol 125: 357–364PubMedGoogle Scholar
  36. Connolly GP (1995) Differentiation by pyridoxal 5-phosphate, PPADS and isoPPADS between responses mediated by UTP and those evoked by a,ß-methylene-ATP on rat sympathetic-ganglia. Br J Pharmacol 114: 727–731PubMedGoogle Scholar
  37. Conti A, Monopoli A, Gamba M, Borea PA, Ongini E (1993) Effects of selective A1 and A2 adenosine receptor agonists on cardiovascular tissues. Naunyn-Schmiedebergs Arch Pharmacol 348: 108–112PubMedGoogle Scholar
  38. Coutinho-Silva R, Persechini PM, Bisaggio RD, Perfettini JL, Neto AC, Kanellopoulos JM, Motta-Ly I, Dautry-Varsat A, OjciusDM (1999) P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Am J Physiol 276: C1139–1147Google Scholar
  39. Cristalli G, Eleuteri A, Vittori S, Volpini R, Lohse MJ, Klotz KN (1992) 2-Alkynyl derivatives of adenosine and adenosine-5’-N-ethyluronamide as selective agonists at A2 adenosine receptors. J Med Chem 35: 2363–2368Google Scholar
  40. Cunha RA, Constantino MD, Ribeiro JA (1997) ZM 241385 is an antagonist of the facilitatory responses produced by the A2A adenosine receptor agonists CGS 21680 and HENECA in the rat hippocampus. Br J Pharmacol 122: 1279–1284PubMedGoogle Scholar
  41. Cunha RA, Johansson B, Constantino MD, Sebastiao AM, Fredholm BB (1996) Evidence for high-affinity binding sites for the adenosine A2A receptor agonist [3H]CGS 21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors. Naunyn-Schmiedebergs Arch Pharmacol 353: 261271Google Scholar
  42. Cusack NJ, Hourani SMO (1990) Structure activity relationships for adenine nucleotide receptors on mast cells, human platelets, and smooth muscle, in Purines in Cellular Signalling: Targets for New Drugs, Jacobson, KA, Daly, JW, Manganiello, V, eds, Springer, New York, pp. 254–259Google Scholar
  43. Daly JW, Padgett WL (1992) Agonist activity of 2- and 5’-substituted adenosine analogs and their N6-cycloalkyl derivatives at A1- and A2-adenosine receptors coupled to adenylate cyclase. Biochem Pharmacol 43: 1089–1093PubMedGoogle Scholar
  44. Daly JW, Butts-Lamb P, Padgett WL (1983) Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cel Mol Neurobiol 3:69 —80Google Scholar
  45. De Zwart M, Vollinga RC, Beukers MW, Sleegers DF, Von Frijtag Drabbe Kunzel J, De Groote M, IJzerman AP (1999) Potent antagonists for the human adenosine A2B receptor. Derivatives of the triazolotriazine adenosine receptor antagonist ZM241385 with high affinity. Drug Dev Res 48: 95–103Google Scholar
  46. Di Virgilio F, Pizzo P, Zanovello P, Bronte V, Collavo D (1990) Extracellular ATP as a possible mediator of cell-mediated cytotoxicity. Immunol Today 11: 274–277PubMedGoogle Scholar
  47. Donaldson SH, Boucher RC (1998) Therapeutic applications for nucleotides in lung disease. Chapter 15 in The P2 Nucleotide Receptors, in the series “The Receptors”, eds. John T. Turner, Gary Weisman, and Jeffrey Fedan, Humana Press, Clifton, NJ, pp. 413–424Google Scholar
  48. Dunwiddie TV, Diao L, Kim HO, Jiang J-L, Jacobson KA (1997) Activation of hippocampal adenosine A3 receptors produces a desensitization of Al receptor-mediated responses in rat hippocampus. J Neurosci 17: 607–614PubMedGoogle Scholar
  49. Dunwiddie TV, Worth T (1982) Sedative and anticonvulsant effects of adenosine analogs in mouse and rat. J Pharm Exp Ther 220: 70–76Google Scholar
  50. Dunwiddie TV, Worth TS, Olsson, RA (1986) Adenosine analogs mediating depressant effects on synaptic transmission in rat hippocampus: structure—activity relation-ships for the Nb subregion. Naunyn-Schmiedebergs Arch Pharmacol 334: 77–85PubMedGoogle Scholar
  51. Eltze M, Ullrich B, (1996) Characterization of vascular P2 purinoceptors in the rat isolated perfused kidney. Eur J Pharmacol 306: 139–152PubMedGoogle Scholar
  52. Feoktistov I, Biaggioni I (1997) Adenosine A2B receptors. Pharmacol Rev 49:381–402 Ferrari D, Stroh C, Schulze-Osthoff K (1999) P2X7/P2Z purinoreceptor-mediated activation of transcription factor NFAT in microglial cells. J Biol Chem 274: 13205–13210Google Scholar
  53. Filippi S, Amerini S, Maggi M, Natali A, Ledda F (1999) Studies on the mechanisms involved in the ATP-induced relaxation in human and rabbit corpus cavernosum. J Urol 161: 326–331PubMedGoogle Scholar
  54. Filtz TM, Harden TK, Nicholas RA (1997) Structure, pharmacological selectivity and second messenger properties of G protein coupled P2 purinergic receptors. In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics. Wiley-Liss, New York pp. 39–53Google Scholar
  55. Fischer B, Boyer JL, Hoyle CHV, Ziganshin AU, Brizzolara AL, Knight GE, Zimmet J, Burnstock G, Harden TK, Jacobson KA (1993) Identification of potent, selective P2Y-purinoceptor agonists — structure—activity relationships for 2-thioether derivatives of adenosine 5’-triphosphate. J Med Chem 36: 3937–3946PubMedGoogle Scholar
  56. Fischer Y, Becker C, Loken C (1999) Purinergic inhibition of glucose transport in cardiomyocytes. J Biol Chem 274: 755–761PubMedGoogle Scholar
  57. Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden KT, Jacobson KA, Leff P, Williams M (1994) Nomenclature and classification of purinoceptors: a report from the IUPHAR subcommittee. Pharmacol Rev 46: 143–156PubMedGoogle Scholar
  58. Fredholm BB, Lindstrom K, Dionisotti S, Ongini E (1998) [3H]SCH 58261, a selective adenosine A2A receptor antagonist, is a useful ligand in autoradiographic studies. J Neurochem 70: 1210–1216Google Scholar
  59. Freissmuth M, Boehm S, Beindl W, Nickel P, lJzerman AP, Hohenegger M, Nanoff C, (1996) Suramin analogues as subtype selective G protein inhibitors. Mol Pharmacol 49: 602–611PubMedGoogle Scholar
  60. Froehlich R, Boehm S, 111es P (1996) Pharmacological characterization of P2 purinoceptor types in rat locus ceruleus neurons. Eur J Pharmacol 315: 255–261Google Scholar
  61. Gallo-Rodriguez C, Ji XD, Melman N, Siegman BD, Sanders LH, Orlina J, Pu QL, Olah ME, van Galen PJM, Stiles GL, Jacobson KA (1994) Structure—activity relationships of N6-benzyladenosine-5’-uronamides as A3-selective adenosine agonists. J Med Chem 37: 636–646PubMedGoogle Scholar
  62. Gargett CE, Wiley JS (1997) The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol 120: 1483–1490PubMedGoogle Scholar
  63. Geiger JD, Parkinson FE, Kowaluk E (1997) Regulators of endogenous adenosine levels as therapeutic agents In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics. Wiley-Liss, New York pp. 55–84Google Scholar
  64. Gellai M, Schreiner GF, Ruffolo RR Jr, Fletcher T, DeWolf R, Brooks DP (1998) CVT124, a novel adenosine A, receptor antagonist with unique diuretic activity. J Pharmacol Exp Ther 286: 1191–1196PubMedGoogle Scholar
  65. Goncalves ML, Ribeiro JA (1996) Adenosine A2 receptor activation facilitates 45Ca’ uptake by rat brain synaptosomes. Eur J Pharmacol 310: 257–261PubMedGoogle Scholar
  66. Grondin R, Bedard P, Tahar A, Hadj GL, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52: 1673–1677PubMedGoogle Scholar
  67. Gurden MF, Coates J, Ellis F, Evans B, Foster M, Hornby E, Kennedy I, Martin DP, Strong P, Vardey CJ, Wheeldon A (1993) Functional characterization of three adenosine receptor types. Br J Pharmacol 109: 693–698PubMedGoogle Scholar
  68. Haleen SJ, Steffen RP, Hamilton HW (1987) PD 116,948, a highly selective A, adenosine receptor antagonist. Life Sci 40: 555–561PubMedGoogle Scholar
  69. He Z, Raman S, Guo Y, Reenstra WW (1998) Cystic fibrosis transmembrane conductance regulator activation by cAMP-independent mechanisms. Am J Physiol 275: C958 — C966PubMedGoogle Scholar
  70. Hechler B, Vigne P, Leon C, Breittmayer JP, Gachet C, Frelin C (1998) ATP derivatives are antagonists of the P2Y, receptor: similarities to the platelet ADP receptor. Mol Pharmacol 53: 727–733PubMedGoogle Scholar
  71. Heffner TG, Wiley JN, Williams AE, Bruns RF, Coughenour LL, Downs DA (1989) Comparison of the behavioral effects of adenosine agonists and dopamine antagonists in mice. Psychopharmacology 98: 31–37PubMedGoogle Scholar
  72. Heseltine L, Webster JM, Taylor R (1995) Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes. Mol Cell Biochem 144: 147151Google Scholar
  73. Hide I, Padgett WL, Jacobson KA, Daly JW (1992) A2A Adenosine receptors from rat striatum and rat pheochromocytoma PC12 cells: Characterization with radioligand binding and by activation of adenylate cyclase. Mol Pharmacol 41: 352359Google Scholar
  74. Humphries RG, Leff P, Robertson MJ (1996) P2T-purinoceptor antagonists: a novel class of anti-thrombotic agents. Drug Dev Res 37: 175Google Scholar
  75. Hutchison AJ, Webb RL, Oei HH, Ghai GR, Zimmerman MB, Williams M (1989) CGS 21680 C, an A2 selective adenosine receptor agonist with preferential hypotensive activity. J Pharmacol Exp Ther 251: 47–55PubMedGoogle Scholar
  76. Hutchison AJ, Williams M, De Jesus R, Yokoyama R, Oei HH, Ghai GR, Webb RL, Zoganas HC, Stone GA, Jarvis MF (1990) 2-(Arylalkylamino)adenosin-5’uronamides: a new class of highly selective adenosine A2 receptor ligands. J Med Chem 33: 1919–1924Google Scholar
  77. IJzerman AP, van der Wenden N (1997) Modulators of adenosine uptake, release, and inactivation. In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics. Wiley-Liss, New York, pp. 129–148Google Scholar
  78. Ikeuchi Y, Nishizaki T (1996) P2 purinoceptor-operated potassium channel in rat cerebellar neurons. Biochem Biophys Res Commun 218: 67–71PubMedGoogle Scholar
  79. Ingall AH, Dixon J, Bailey A, Coombs ME, Cox D, Mclnally JI, Hunt SF, Kindon ND, Teobald BJ, Willis PA, Humphries RG, Leff P, Clegg JA, Smith JA, Tomlinson W (1999) Antagonists of the Platelet P2T Receptor: A Novel Approach to Antithrombotic Therapy. J Med Chem. 42: 213–220Google Scholar
  80. Inscho EW, Cook AK, Mui VY, Miller J (1998) Direct assessment of renal microvascular responses to P2-purinoceptor agonists. Am J Physiol 274: F718 — F727PubMedGoogle Scholar
  81. Ishikawa J, Mitani H, Bandoh T, Kimura M, Totsuka T, Hayashi S (1998) Hypoglycemic and hypotensive effects of 6-cyclohexyl-2’-O-methyl-adenosine, an adenosine A, receptor agonist, in spontaneously hypertensive rat complicated with hyperglycemia. Diabetes Res Clin Pract 39: 3–9PubMedGoogle Scholar
  82. Jacobson KA, Barone S, Kammula U, Stiles GL (1989) Electrophilic derivatives of purines as irreversible inhibitors of A, adenosine receptors. J Med Chem 32: 1043–1051PubMedGoogle Scholar
  83. Jacobson KA, Gallo-Rodriguez C, Melman N, Fischer B, Maillard M, van Bergen A, van Galen PJM, Karton Y (1993a) Structure—activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists. J Med Chem 36: 1333–1342PubMedGoogle Scholar
  84. Jacobson KA, Guay-Broder C, van Galen PJM, Gallo-Rodriguez C, Melman N, Jacob-son, MA, Eidelman O, Pollard HB (1995) Stimulation by alkylxanthines of chloride efflux in CFPAC-1 cells does not involve A, adenosine receptors. Biochemistry 34: 9088–9094PubMedGoogle Scholar
  85. Jacobson KA, Hoffmann C, Kim YC, Camaioni E, Nandanan E, Jang SY, Guo DP, Ji X-D, von Kugelgen I, Moro S, King BF, Brown SG, Wildman SS, Burnstock G, Boyer JL, Mohanram A, TK Harden (1999) Molecular recognition in P2 receptors: Ligand development aided by molecular modeling and mutagenesis. Prog Brain Res. 120: 119–132Google Scholar
  86. Jacobson KA, IJzerman AP, Linden, J (1999) 1,3-Dialkylxanthine derivatives having high potency as antagonists at human A2B receptors. Drug Dev Res 47: 45–53Google Scholar
  87. Jacobson KA, Kim HA, Siddiqi SM, Olah ME, Stiles GL, von Lubitz DKJE (1995) A3 adenosine receptors: design of selective ligands and therapeutic prospects. Drugs Fut 20: 689–699Google Scholar
  88. Jacobson KA, Kim Y-C, Camaioni E, van Rhee, AM (1997a) Structure activity relationships of P2 receptor agonists and antagonists. In: Turner JT, Weisman G, Fedan J (eds) The P2 Nucleotide Receptors. Humana Press, Clifton NJ, pp. 81107Google Scholar
  89. Jacobson KA, Kim Y-C, Wildman SS, Mohanram A, Harden TK, Boyer JL, King BF, Burnstock G (1998) A pyridoxine cyclic-phosphate and its 6-arylazo-derivative selectively potentiate and antagonize activation of P2X, receptors. J Med Chem 41: 2201–2206PubMedGoogle Scholar
  90. Jacobson KA, Kirk KL, Padgett WL, Daly JW (1985) Functionalized congeners of adenosine: preparation of analogs with high affinity for A,-adenosine receptors. J Med Chem 28: 1341–1346PubMedGoogle Scholar
  91. Jacobson KA, Nikodijevic O, Padgett WL, Gallo-Rodriguez C, Maillard M, Daly JW (1993b) 8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo. FEBS Lett 323: 141–144Google Scholar
  92. Jacobson KA, Pannell LK, Ji XD, Jarvis MF, Williams M, Hutchison AJ, Barrington WW, Stiles GL (1989) Agonist derived molecular probes for A2 adenosine receptors. J Mol Recognit 2: 170–178PubMedGoogle Scholar
  93. Jacobson KA, Park K-S, Jiang J-L, Kim Y-C, Olah ME, Stiles GL, Ji X-D (1997b) Pharmacological characterization of novel A3 adenosine receptor-selective antagonists. Neuropharmacology 36: 1157–1165PubMedGoogle Scholar
  94. Jacobson KA, van Rhee AM (1997) Development of Selective Purinoceptor Agonists and Antagonists. In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics. Wiley-Liss, New York, pp 101–128Google Scholar
  95. Jacobson MA (1998) Novel selective non-xanthine A3 adenosine receptor antagonists. Book of Abstracts, 215th ACS National Meeting, Dallas, March 29-April 2: MEDI095Google Scholar
  96. Janusz CA, Berman RF (1993) Adenosinergic modulation of the EEG and locomotor effects of the A2 agonist CGS 21680. Pharm Biochem Behav 45: 913–919Google Scholar
  97. Jarvis MF, Schultz R, Hutchison AJ, Do UH, Sills MA, Williams M (1989) [3H1-CGS 21680, a selective A2 adenosine receptor agonist directly labels A, receptors in rat brain. J Pharmacol Exp Ther 251: 888–893Google Scholar
  98. Jarvis MF, Williams M, Do UH, Sills MA (1991) Characterization of the binding of a novel nonxanthine adenosine antagonist radioligand, [3H]CGS 15943, to multiple affinity states of the adenosine A, receptor in the rat cortex. Mol Pharmacol 39: 49–54PubMedGoogle Scholar
  99. Ji X-D, Jacobson KA (1999) Use of the triazolotriazine [3H]ZM 241385 as a radioligand at recombinant human A2B adenosine receptors. Drug Des Discovery 16: 217–226Google Scholar
  100. Jiang J-1, van Rhee AM, Melman N, Ji X-D, Jacobson KA (1996) 6-Phenyl-1,4dihydropyridine derivatives as potent and selective A3 adenosine receptor antagonists. J Med Chem 39: 4667–4675Google Scholar
  101. Johansson B, Fredholm BB (1995) Further characterization of the binding of the adenosine receptor agonist [3H]CGS 21680 to rat brain using autoradiography. Neuropharmacology 34: 393–403PubMedGoogle Scholar
  102. Jones PA. Smith RA, Stone TW (1998a) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85: 229–237PubMedGoogle Scholar
  103. Jones PA, Smith RA, Stone TW (1998b) Protection against hippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800: 328–335PubMedGoogle Scholar
  104. Kanda T,Tashiro T, Kuwana Y, Jenner P (1998) Adenosine A2A receptors modify motor function in MPTP-treated common marmosets. Neuroreport 9: 2857–2860PubMedGoogle Scholar
  105. Kanda T, Jackson MJ, Smith LA, Pearce RKB, Nakamura J, Kase H, Kuwana Y, Jenner P (1998) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys. Ann Neurol 43: 507–513PubMedGoogle Scholar
  106. Kanda T, Tashiro T. Kuwana Y, Jenner P (1998) Adenosine A2A receptors modify motor function in MPTP-treated common marmosets. Neuroreport 9: 2857–2860PubMedGoogle Scholar
  107. Keddie JR, Poucher SM, Shaw GR, Brooks R, Collis MG (1996) In vivo characterization of ZM 241385, a selective adenosine A2A receptor antagonist. Eur J Pharmacol 301:107–113Google Scholar
  108. Kennedy C, Leff P (1995) How should P2X purinoceptors be classified pharmacologically. Trends Pharmacol Sci 16: 168–174PubMedGoogle Scholar
  109. Kennedy C, Qi A-I, Herold CL, Harden TK, Nicholas RA (2000) ATP, an agonist at the rat P2Y4 receptor, is an antagonist at the human P2Y4 receptor. Mol. Pharmacol 57: 926–931Google Scholar
  110. Khakh BS, Zhou X, Sydes J, Galligan JJ, Cester HA (2000) State-dependent cross-inhibition between transmitter-gated cation channels. Nature 406: 405–410PubMedGoogle Scholar
  111. Kikugawa K, Iizuka K, Ichino M (1973) Platelet aggregation inhibitors. 4. N°-Substituted adenosines. J Med Chem 16: 358–364PubMedGoogle Scholar
  112. Kim Y-C, Ji, X-d, Melman N, Linden J, Jacobson KA (2000) Anilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A2B adenosine receptors. J Med Chem 43: 1165–1172PubMedGoogle Scholar
  113. Kim HO Ji, X-d, Siddiqi SM. Olah ME, Stiles GL, Jacobson KA (1994) 2-Substitution of N6-Benzyladenosine-5’-uronamides Enhances Selectivity for A3 Adenosine Receptors. J Med Chem 37: 3614–3621Google Scholar
  114. Kim YC, Camaioni E, Ziganshin AU, Ji XJ, King BF, Wildman SS, Rychkov A, Yoburn J, Kim H, Mohanram A, Harden TK, Boyer JL, Burnstock G, Jacobson KA (1998) Synthesis and structure activity relationships of pyridoxal-6-azoaryl-5’-phosphate and phosphonate derivatives as P2 receptor antagonists. Drug Dev Res 45: 52–66PubMedGoogle Scholar
  115. Kim Y-C, Ji X-D, Jacobson KA (1996) Derivatives of the triazoloquinazoline adenosine antagonist (CGS 15943) are selective for the human A3 receptor subtype. J Med Chem 39: 4142–4148PubMedGoogle Scholar
  116. King, BF, Liu, M. Pintor, J. Gualix J, Miras-Portugal MT, Burnstock G. (1999) Diinosine pentaphosphate (Ipsl) is a potent antagonist at recombinant rat P2X, receptors. Br J Pharmacol 128: 981–988Google Scholar
  117. Klitgaard H, Knutsen US, Thomsen C (1993) Contrasting effects of adenosine A, and A2 receptor ligands in different chemoconvulsive models. Eur J Pharmacol 224: 221–228Google Scholar
  118. Klotz K-N, Hessling J, Hegler J, Owman C, Kull B, Fredholm BB, Lohse MJ (1998) Comparative pharmacology of human adenosine receptor subtypes — characterization of stably transfected receptors in CHO cells. Naunyn-Schmiedebergs Arch Pharmacol 357: 1–9PubMedGoogle Scholar
  119. Knutsen US, Lau J, Petersen H, Thomsen C, Weis JU, Shalmi M, Judge ME, Hansen A, Sheardown MJ (1999) N-Substituted adenosines as novel neuroprotective A, agonists with diminished hypotensive effects. J Med Chem 41: 3463–3477Google Scholar
  120. Knutsen US, Lau J, Eskesen K, Sheardown MJ, Thomsen C, Weis JU, Judge ME, Klitgaard H (1995) Anticonvulsant actions of novel and reference adenosine agonists. In Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology, Belardinelli L and Pelleg A Eds Kluwer, Boston MA, pp. 479–487Google Scholar
  121. Knutsen US, Murray TF (1997) Adenosine and ATP in Epilepsy. In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics. Wiley-Liss, New York, 1997, pp. 423–447Google Scholar
  122. Knutsen US, Sheardown MJ, Roberts SM, Mogensen JP, Olsen UB,Thomsen C, Bowler AN (1998) Adenosine A, and A3 Selective N-Alkoxypurines as novel Cytokine Modulators and Neuroprotectants. Drug Dev Res 45: 214–221Google Scholar
  123. Kohno Y, Sei Y, Koshiba M, Kim HO, Jacobson KA (1996) Induction of apoptosis in HL-60 human promyelocytic leukemia cells by adenosine A3 receptor agonists. Biochem Biophys Res Commun 219: 904–910PubMedGoogle Scholar
  124. Koizumi S, Inoue K (1997) Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurons. Br J Pharmacol 122: 51–58PubMedGoogle Scholar
  125. Krahl SE, Treas LM, Castle JD, Berman RF (1995) Attenuation of in vivo and in vitro seizure activity using the adenosine agonist metrifudil. Drug Dev Res 34: 30–34Google Scholar
  126. Kugler G, Westermann KW II (1974) Effects of adenosine on metabolic and electrocardiographic parameters during a trial pacing in patients with coronary heart disease. Z Kardiol 63: 987–1000PubMedGoogle Scholar
  127. Lazarowski ER, Watt WC, Stutts MJ, Brown HA, Boucher RC, Harden TK (1996) Enzymatic-synthesis of UTP-g-S, a potent hydrolysis resistant agonist of P2Upurinoceptors. Br J Pharmacol 117: 203–209PubMedGoogle Scholar
  128. Lindstroem K, Ongini E, Fredholm, BB (1996) The selective adenosine A2A receptor antagonist SCH 58261 discriminates between two different binding sites for EH]-CGS 21680 in the rat brain. Naunyn-Schmiedebergs Arch Pharmacol 354: 539–541Google Scholar
  129. Louttit JB, Hunt AAE, Maxwell MP, Drew GM (1999) The time course of cardioprotection induced by GR79236, a selective adenosine A,-receptor agonist, in myocardial ischemia-reperfusion injury in the pig. J Cardiovasc Pharmacol 33: 285–291PubMedGoogle Scholar
  130. Lozza G, Conti A, Ongini E, Monopoli A (1997) Cardioprotective effects of adenosine A, and A2A receptor agonists in the isolated rat heart. Pharmacol Res 35: 57–64PubMedGoogle Scholar
  131. Macgregor DG, Graham DI, Jones PA, Stone TW (1998) Protection by an adenosine analog against kainate-induced extrahippocampal neuropathology. Gen Pharmacol 31: 233–238PubMedGoogle Scholar
  132. Malcolm KC, Trammell SE, Exton JH (1995) Purinergic agonist and G protein stimulation of phospholipase D in rat liver plasma membranes. Independence from phospholipase C activation. Biochim Biophys Acta 1268: 152–158Google Scholar
  133. Mally J, Stone TW (1998) Potential of adenosine A2A receptor antagonists in the treatment of movement disorders. CNS Drugs 10: 311–320Google Scholar
  134. Martin PL, Wysocki RJ Jr, Barrett RJ, May JM, Linden J (1996) Characterization of 8-(N-methylisopropyl)amino-N6-(5’-endohydroxy-endonorbornyl)-9-methylade-nine (WRC-0571), a highly potent and selective, non-xanthine antagonist of Al adenosine receptors. J Pharmacol Exp Ther 276: 490–499PubMedGoogle Scholar
  135. Mathot RAA, van Den Aarsen FM, Soudijn W, Breimer DD, IJzerman AP, Danhof M (1995) Pharmacokinetic-pharmacodynamic modeling of the cardiovascular effects of R- and S-N6-phenylisopropyladenosine in conscious normotensive rats. J Pharmacol Exp Ther 273: 405–414PubMedGoogle Scholar
  136. Merkel LA, Hawkins ED, Colussi DJ, Greenland BD, Smits GJ, Perrone MH, Cox BF (1995) Cardiovascular and antilipolytic effects of the adenosine agonist GR 79236. Pharmacology 51: 224–236PubMedGoogle Scholar
  137. Michel AD, Lundstroem K, Buell GN, Surprenant A, Valera S, Humphrey PPA (1996) A comparison of the binding characteristics of recombinant P2X, and P2X2 purinoceptors. Br J Pharmacol 118: 1806–1812PubMedGoogle Scholar
  138. Mogensen JP, Roberts SM, Bowler AN, Thomsen C, Knutsen LJS (1998) The Synthesis Of New Adenosine A3 Selective Ligands Containing Bioisosteric Isoxazoles. Bioorg Med Chem Lett 8: 1767–1770PubMedGoogle Scholar
  139. Monopoli A, Conti A, Zocchi C, Casati C, Volpini R, Cristalli G, Ongini E (1994) Pharmacology of the new selective Ala adenosine receptor agonist 2-hexynyl-5’N-ethylcarboxamidoadenosine. Arzneim -Forsch 44: 1296–1304Google Scholar
  140. Moos H, Szotek DS, Bruns RF (1985) N6-Cycloalkyladenosines. Potent, A,-selective adenosine agonists. J Med Chem 28: 1383–1384Google Scholar
  141. Nakazawa K, Inoue K, Ito K, Koizumi S (1995) Inhibition by suramin and reactive blue 2 of GABA and glutamate receptor channels in rat hippocampal neurons. NaunynSchmiedebergs Arch Pharmacol 351: 202–208Google Scholar
  142. Nandanan E, Camaioni E, Jang SY, Kim Y-C, Cristalli G, Herdewijn P, Secrist, JA, Tiwari KN, Mohanram A, Harden TK, Boyer JL, and Jacobson KA (1999) Structure activity relationships of bisphosphate nucleotide derivatives as P2Y, receptor antagonists and partial agonists. J Med Chem 42: 1625–1638PubMedGoogle Scholar
  143. Neely CF, DiPierro FV, Kong M, Greelish JP, Gardner TJ (1996) A, adenosine receptor antagonists block ischemia-reperfusion injury of the heart. Circulation Suppl 94: I1376–11380Google Scholar
  144. Nikodijevic O, Daly JW, Jacobson KA (1990) Characterization of the locomotor depression produced by an A2-selective adenosine agonist. FEBS Lett: 261: 67–70PubMedGoogle Scholar
  145. North RA, Barnard EA (1997) Nucelotide receptors, Current Opinion in Neurobiol-ogy 7: 346–357Google Scholar
  146. Olah ME, Gallo-Rodriguez C, Jacobson KA, Stiles GL (1994) 725I-4-aminobenzyl-5’-Nmethylcarboxamido adenosine, a high affinity radioligand for the rat A3 adenosine receptor. Mol Pharmacol 45: 978–982Google Scholar
  147. Olsson RA, Kusachi S, Thompson RD, Ukena D, Padgett W, Daly JW (1986) N6-Substituted N-alkyladenosine-5’-uronamides: bifunctional ligands having recognition groups for A, and A2 adenosine receptors. J Med Chem 29: 1683–1689PubMedGoogle Scholar
  148. Ongini E (1997) SCH 58261: a selective A2A adenosine receptor antagonist. Drug Dev Res 42: 63–70Google Scholar
  149. Ongini E, Adami M, Ferri C, Bertorelli R (1998) Adenosine A2A receptors and Neuroprotection. Ann NY Acad Sci 30–48Google Scholar
  150. Palmer RK, Boyer JL, Schachter JB, Nicholas RA, Harden TK (1998) Agonist action of adenosine triphosphates at the human P2Y, receptor. Mol Pharmacol 54: 1118–1123PubMedGoogle Scholar
  151. Palmer TM, Poucher SM, Jacobson KA, Stiles GL (1995) ‘2’I-4(2-[7-amino-2-{2fury1}{1,2,41triazolo{2,3-a111,3,5}triazin-5-yl-aminojethyl)phenol, a high affinity antagonist radioligand selective for the A2, adenosine receptor. Mol Pharmacol 48: 970–974Google Scholar
  152. Petit P, Hillaire-Buys D, Manteghetti M, Debrus S, Chapal J, Loubatieres-Mariani MM (1998) Evidence for two different types of P2 receptors stimulating insulin secretion from pancreatic B cell. Br J Pharmacol 125: 1368–1374PubMedGoogle Scholar
  153. Pfister JR, Belardinelli L, Lee G, Lum RT, Milner P, Stanley WC, Linden J, Baker SP, Schreiner G (1997) Synthesis and Biological Evaluation of the Enantiomers of the Potent and Selective A,-Adenosine Antagonist 1,3-Dipropy1–8-[2-(5,6-epoxy)norbonyl1- xanthine. J Med Chem 40: 1773–1778PubMedGoogle Scholar
  154. Pintor J, Puche JA, Gualix J, Hoyle CHV, Miras-Portugal MT (1997) Diadenosine polyphosphates evoke Ca’ transients in guinea — pig brain via receptors distinct from those for ATE J Physiol. ( Cambridge. UK ) 504: 327–335Google Scholar
  155. Popoli P, Reggio R, Pezzola A, Fuxe K, Ferre S (1998) Adenosine A, and A2A receptor antagonists stimulate motor activity: evidence for an increased effectiveness in aged rats. Neurosci Lett 251: 201–204PubMedGoogle Scholar
  156. Poucher SM, Keddie JR, Brooks R, Shaw GR, McKillop D (1996) Pharmacodynamics of ZM 241385, a potent A2, adenosine receptor antagonist, after enteric administration in rat, cat and dog. 4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) is currently the most selective for the Ala adenosine receptor antagonist. J Pharm Pharmacol 48: 601606Google Scholar
  157. Poucher SM, Keddie JR, Singh P, Stoggall SM, Caulkett PWR, Jones G, Collis MG (1995) The in vitro pharmacology of ZM 241385, a potent, non-xanthine, Aza selective adenosine receptor antagonist. Br J Pharmacol 115: 1096–1102PubMedGoogle Scholar
  158. Poulsen S-A, Quinn RJ (1998) Adenosine receptors: new opportunities for future drugs. Bioorg Med Chem 6: 619–641PubMedGoogle Scholar
  159. Raberger G, Schuetz W, Kraupp 0 (1977) Coronary dilatory action of adenosine analogs: a comparative study. Arch Int Pharmacodyn Ther 230: 140–149Google Scholar
  160. Rae MG, Rowan EG, Kennedy C (1998) Pharmacological properties of P2X3receptors present in neurons of the rat dorsal root ganglia. Br J Pharmacol 124: 176–180PubMedGoogle Scholar
  161. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev. 50: 413–492PubMedGoogle Scholar
  162. Ribes G, Bertrand G, Petit P, Loubatieres-Mariani MM (1988) Effects of 2-methylthio ATP on insulin secretion in the dog in vivo. Eur J Pharmacol 155: 171–174PubMedGoogle Scholar
  163. Rivkees SA, Reppert SM (1992) RFL9 encodes an Azh-adenosine receptor. Mol Endocrinol 6: 1598–1604PubMedGoogle Scholar
  164. Robertson SJ, Edwards FA (1998) ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine-mediated inhibition of release. J Physiol (Lond) 508: 691–701Google Scholar
  165. Ross FM, Brodie MJ, Stone TW (1998) Modulation by adenine nucleotides of epileptiform activity in the CA3 region of rat hippocampal slices. Br J Pharmacol 123: 71–80PubMedGoogle Scholar
  166. Rubino A, Burnstock G (1996) Evidence for a P2-purinoceptor mediating vasoconstriction by UTP, ATP and related nucleotides in the isolated pulmonary vascular bed of the rat. Br J Pharmacol 118: 1415–1420Google Scholar
  167. Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB (1992) Neuroprotective role of adenosine in cerebral ischaemia. Trends Pharmacol Sci 13: 439–445PubMedGoogle Scholar
  168. Sajjadi FG, Takahayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-a expression by adenosine. Role of A3 adenosine receptors. J Immunol 156: 3435–3442PubMedGoogle Scholar
  169. Sansum AJ, Chessell IP, Hicks GA, Trezise DJ, Humphrey PPA (1998) Evidence that P2X purinoceptors mediate the excitatory effects of a,ß-methylene-ADP in rat locus ceruleus neurons. Neuropharmacology 37: 875–885PubMedGoogle Scholar
  170. Satoh S, Matsumura H, Hayaishi 0 (1998) Involvement of adenosine AzA receptor in sleep promotion. Eur J Pharmacol 351: 155–162Google Scholar
  171. Schaumann E, Kutscha W (1972) Clinical-pharmacological studies with a new orally active adenosine derivative. Drug Res 22: 783–790Google Scholar
  172. Schaumann E, Schlierf G, Pfleiderer T, Weber E (1972) Effect of repeated doses of phenylisopropyladenosine on lipid and carbohydrate metabolism in healthy fasting subjects. Arzneim-Forsch 22: 593–596Google Scholar
  173. Schingnitz G, Kuefner-Muehl U, Ensinger H, Lehr E, Kuhn FJ (1991) Selective A,-antagonists for treatment of cognitive deficits. Nucleosides Nucleotides 10: 10671076Google Scholar
  174. Schwabe U, Trost T (1980) Characterization of adenosine receptors in rat brain by (—) [3H11\16-phenylisopropyladenosine. Naunyn-Schmiedebergs Arch Pharmacol 313: 179–187PubMedGoogle Scholar
  175. Sei Y, von Lubitz DKJE, Abracchio MP, Ji XD, Jacobsen KA (1997) Adenosine A3 receptor agonist-induced neurotoxicity in rat cerebellar granule neurons. Drug Dev Res 40: 267–273Google Scholar
  176. Sheardown MJ, Hansen AJ, Thomsen C, Judge ME, Knutsen LJS (1985) Novel adenosine agonists: a strategy for stroke therapy. In: Grotta J, Miller L, Buchan AM, (eds) Ischemic Stroke: Recent Advances in Understanding and Therapy. International Business Communications pp. 187–214Google Scholar
  177. Sheardown MJ, Knutsen LJS (1996). Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS 21680. Drug Dev Res 39: 108–114Google Scholar
  178. Shearman LP, Weaver DR (1997) [125I]14-Aminobenzyl-5’-N-methylcarboxamidoadenosine (rI1AB-MECA) labels multiple adenosine receptor subtypes in rat brain. Brain Res 745: 10–20Google Scholar
  179. Shibuya I, Tanaka K, Hattori Y, Uezono Y, Harayama N, Noguchi J, Ueta Y, Izumi F, Yamashita H (1999) Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones. J Physiol (Lond) 514 (Pt 2): 351–367Google Scholar
  180. Shimada J, Koike N, Nonaka H, Shiozaki S, Yanagawa K, Kanda T, Kobayashi H, Ichimura, M, Nakamura J, Kase H, Suzuki F (1997) Adenosine A2A antagonists with potent anti-cataleptic activity. Bioorg Med Chem Lett 7: 2349–2352Google Scholar
  181. Shneyvays V, Nawrath H, Jacobson KA, Shainberg A (1998) Induction of apoptosis in cardiac myocytes by an A3 adenosine receptor agonist. Exp Cell Res 243: 383–397PubMedGoogle Scholar
  182. Shryock JC, Ozeck MJ, Belardinelli L (1998) Inverse agonists and neutral antagonists of recombinant human A, adenosine receptors stably expressed in Chinese hamster ovary cells. Mol Pharmacol 53: 886–893PubMedGoogle Scholar
  183. Siddiqi SM, Jacobson KA, Esker JL, Olah ME, Li X-D, Melman N, Tiwari KN, Secrist III, JA, Schneller S, Cristalli G, Stiles GL, Johnson CR, IJzerman AP (1995) Search for new purine-and ribose-modified adenosine analogues as selective agonists and antagonists at adenosine receptors. J Med Chem 38: 1174–1178PubMedGoogle Scholar
  184. Soltoff SP, McMillian MK, Talamo BR (1989) Coomassie brilliant blue G is a more potent antagonist of P2 purinergic responses than reactive blue 2 (cibacron blue 3GA) in rat parotid acinar cells. Biochem Biophys Res Commun 165: 1279–1285PubMedGoogle Scholar
  185. Song SL, Chueh SH (1996) P2 purinoceptor-mediated inhibition of cyclic AMP accumulation in NG108–15 cells. Brain Res 734: 243–251PubMedGoogle Scholar
  186. Stoop R, Surprenant A, North RA (1997) Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors. J Neurophysiol 78: 1837–1840PubMedGoogle Scholar
  187. Strong P, Anderson R, Coates J, Ellis F, Evans B, Gurden MF, Johnstone J, Kennedy I Martin DP (1993). Suppression of non-esterified fatty acids and triacylglycerol in experimental animals by the adenosine analog GR79236. Clin Sci 84: 663–669PubMedGoogle Scholar
  188. Thomsen C, Valsborg JS, Foged C, Knutsen US (1997) Characterization of [3H1-N-[R(2-Benzothiazolyl)thio-2-propyll-2-chloroadenosine ([3H1-NNC 21–0136) binding to rat brain: profile of a novel selective adenosine receptors for adenosine Al receptors. Drug Dev Res 42: 86–97Google Scholar
  189. Trivedi BK, Bruns RF (1989) C2,N6-Disubstituted adenosines: synthesis and structure—activity relationships. J Med Chem 32: 1667–1673PubMedGoogle Scholar
  190. Tuluc F, Bultmann R, Glanzel M, Frahm AW, Starke K (1998) P2-receptor antagonists: IV. Blockade of P2-receptor subtypes and ecto-nucleotidases by compounds related to reactive blue 2. Naunyn-Schmiedebergs Arch Pharmacol 357: 11 1120Google Scholar
  191. Ukena D, Jacobson KA, Padgett WL, Ayala C, Shamim MT, Kirk KL, Olsson RA, Daly JW (1986) Species differences in structure—activity relationships of adenosine agonists and xanthine antagonists at brain A, adenosine receptors. FEBS Lett 209: 122–128PubMedGoogle Scholar
  192. Uneyama H, Uneyama C, Ebihara S, Akaike, N (1994) Suranim and reactive blue 2 are antagonists for a newly identified purinoceptor on rat megakaryocyte. Br J Pharmacol 111: 245–249PubMedGoogle Scholar
  193. Usune S, Katsuragi T, Furukawa T (1996) Effects of PPADS and suramin on contractions and cytoplasmic Ca’ changes evoked by AP4 A, ATP and a,ß-methylene ATP in guinea pig urinary bladder. Br J Pharmacol 117: 698–702Google Scholar
  194. van Rhee AM, van der Heijden MPA, Beukers MW, IJzerman AP, Soudijn W, Nickel P, (1994) Novel competitive antagonists for P2 purinoceptors. Eur J Pharmacol 268: 1–7PubMedGoogle Scholar
  195. van Schaick EA, Kulkarni C, von Frij tag Drabbe Kunzel JK, Mathot RAA, Cristalli G, IJzerman AP, Danhof M (1997) Time course of action of three adenosine A, receptor agonists with differing lipophilicity in rats: comparison of pharmacokinetic, hemodynamic and EEG effects. Naunyn-Schmiedebergs Arch Pharmacol 356: 827–837Google Scholar
  196. van Schaick EA, Jacobson KA, Kim HO, IJzerman AP, Danhof M (1996) Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats. Eur J Pharmacol 308: 311–314PubMedGoogle Scholar
  197. Varani K, Borea PA, Guerra L, Dionisotti S, Zocchi C, Ongini E (1995) Binding of the adenosine Ala receptor ligand [3H]CGS 21680 to human platelet membranes. Res Commun Mol Pathol Pharmacol 87: 109–110Google Scholar
  198. Varani K, Cacciari B, Baraldi PG, Dionisotti S, Ongini E, Borea PA (1998) Binding affinity of adenosine receptor agonists and antagonists at human cloned A3 adenosine receptors. Life Sci 63:PL81–PL87Google Scholar
  199. Varani K, Merighi S, Gessi S, Klotz KN, Leung E, Baraldi PG, Cacciara B, Romagnoli R, Spalluto G, Borea PA (2000) [3H]MRE 3008F20: A Novel Antagonist Radio-ligand for the Pharmacological and Biochemical Characterization of Human A3 Adenosine Receptors. Mol Pharmacol 57: 968–975Google Scholar
  200. Virginio C, Robertson G, Surprenant A, North RA (1998) Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X,, P2X3, and heteromeric P2X2,3 receptors. Mol Pharmacol 53: 969–973PubMedGoogle Scholar
  201. Volonte C, Merlo D (1997) Biological effects of P2 purinoceptor modulators in cultured primary cerebellar granule neurons. Proc Eur Soc Neurochem Meeting 11: 357–360Google Scholar
  202. von Heijne M, Hao J-X, Yu W, Sollevi A, Xu X-J, Wiesenfeld-Hallin Z (1998) Reduced anti-allodynic effect of the adenosine A,-receptor agonist R-phenylisopropyladenosine on repeated intrathecal administration and lack of cross-tolerance with morphine in a rat model of central pain. Anesth Analg 87: 1367–1371Google Scholar
  203. von Lubitz DKJE, Beenhakker M, Lin RC-S, Carter MF, Paul IA, Bischofberger N, Jacobson KA (1996) Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine Al receptor agonist. Eur J Pharmacol 302: 43–48Google Scholar
  204. von Lubitz DKJE, Lin RC-S, Boyd M, Bischofberger N, Jacobson KA (1999) Chronic administration of adenosine A3 receptor agonist and cerebral ischemia: neuronal and glial effects. Eur J Pharmacol 367: 157–163Google Scholar
  205. von Lubitz DKJE, Lin RCS, Jacobson KA (1995b) Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287: 295–302Google Scholar
  206. von Lubitz DKJE, Lin RC-S, Melman N Ji X-d, Carter MF, Jacobson KA (1994) Chronic administration of selective adenosine A, receptor agonist or antagonist in cerebral ischemia. Eur J Pharmacol 256: 161–167Google Scholar
  207. von Lubitz DKJE, Lin RC-S, Paul IA, Beenhakker M, Boyd M, Bischofberger N, Jacobson KA (1996b) Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. Eur J Pharmacol 316: 171–179Google Scholar
  208. Wainwright CL, Kang L, Ross S (1997) Studies on the mechanism underlying the antifibrillatory effect of the A,-adenosine agonist, R-PIA, in rat isolated hearts. Cardiovasc Drugs Ther 11: 669–678Google Scholar
  209. Wagner H, Milavec-Krizman M, Gadient F, Menninger K, Schoeffter P, Tapparelli C, Pfannkuche H-J, Fozard JR (1995) General pharmacology of SDZ WAG 994, a potent selective and orally active adenosine A, receptor agonist. Drug Dev Res 34: 276–288Google Scholar
  210. Webb RL, Barclay BW, Graybill SC (1991) Cardiovascular effects of adenosine A2 agonists in the conscious spontaneously hypertensive rat: a comparative study of three structurally distinct ligands. J Pharmacol Exp Ther 259: 1203–1212PubMedGoogle Scholar
  211. Wildman SS, Brown SG, King BF, Burnstock G (1999) Selectivity of diadenosine polyphosphates for rat P2X receptor subunits. Eur J Pharmacol 367: 119–123PubMedGoogle Scholar
  212. Wiley S, Gargett CE, Zhang W, Snook MB, Jamieson GP (1998) Partial agonists and antagonists reveal a second permeability state of human lymphocyte P2Z/P2X, channel. Am J Physiol 275: C1224 — C1231PubMedGoogle Scholar
  213. Williams M (1996) Challenges in developing P2 purinoceptor-based therapeutics. Ciba Found Symp 1996, 198: 309–321PubMedGoogle Scholar
  214. Williams M (2000) Purines: From Premise to promise. J. Autonom. Nervous System. In pressGoogle Scholar
  215. Windscheif U, Pfaff O, Ziganshin AU, Hoyle CHV, Bäumert HG, Mutschler E, Burn-stock G, Lambrecht G (1995) Inhibitory action of PPADS on relaxant responses to adenine-nucleotides or electrical-field stimulation in guinea-pig taenia-coli and rat duodenum. Br J Pharmacol 115: 1509–1517PubMedGoogle Scholar
  216. Wolff AA, Skettino SL, Beckman E, Belardinelli L (1998) Renal effects of BG9719, a specific A, adenosine receptor antagonist, in congestive heart failure. Drug Dev Res 45: 166–171Google Scholar
  217. Xu H, Bianchi B, Metzger R, Lynch KJ, Kowaluk EA, Jarvis MF, van Biesen T (1999) Lack of specificity of [35S]-ATP1.S and [35S]-ADPßS as radioligands for inotropic and metabotropic P2 receptor binding. Drug Dev Res 48: 84–93Google Scholar
  218. Yagil Y, Miyamoto M (1995) The hypotensive effect of an oral adenosine analog with selectivity for the Az receptor in the spontaneously hypertensive rat. Am J Hyper-tens 8: 509–515Google Scholar
  219. Yang CM, Tsai YJ, Pan SL, Tsai CT, Wu WB, Chiu CT, Luo SF, Ou JT (1997) Purinoceptor-stimulated phosphoinositide hydrolysis in Madin-Darby canine kidney ( MDCK) cells. Naunyn-Schmiedebergs Arch Pharmacol 356: 1–7Google Scholar
  220. Yao Y, Sei Y, Abbracchio MP, Jiang J-L, Kim Y-C, Jacobson KA (1997) Adenosine A3 receptor agonists protect HL-60 and U-937 cells from apoptosis induced by A3 antagonists. Biochem Biophys Res Commun 232: 317–322PubMedGoogle Scholar
  221. Ziganshin AU, Hoyle C, Bo XN, Lambrecht G, Mutschler E, Bäumert HG, Burnstock G (1993) PPADS selectively antagonizes P2X purinoceptor-mediated responses in the rabbit urinary-bladder. Br J Pharmacol 110: 1491–1495PubMedGoogle Scholar
  222. Zimmet J, Jârlebark L, van Galen PJM, Jacobson, KA, Heilbronn E (1993) Synthesis and biological activity of novel 2-thio derivatives of ATP. Nucleosides Nucleotides 12: 1–20Google Scholar
  223. Ziyal R, Ralevic V, Ziganshin AU, Nickel P, Adanuy U. Mutschler E, Lambrecht G, Burnstock G (1996) NF023, a selective P2X-purinoceptor antagonist in rat hamster and rabbit isolated blood vessels. Drug Dev Res 37: 113Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • K. A. Jacobson
  • L. J. S. Knutsen

There are no affiliations available

Personalised recommendations