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Selectivity is species-dependent: Characterization of standard agonists and antagonists at human, rat, and mouse adenosine receptors

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Abstract

Adenosine receptors (ARs) have emerged as new drug targets. The majority of data on affinity/potency and selectivity of AR ligands described in the literature has been obtained for the human species. However, preclinical studies are mostly performed in mouse or rat, and standard AR agonists and antagonists are frequently used for studies in rodents without knowing their selectivity in the investigated species. In the present study, we selected a set of frequently used standard AR ligands, 8 agonists and 16 antagonists, and investigated them in radioligand binding studies at all four AR subtypes, A1, A2A, A2B, and A3, of three species, human, rat, and mouse. Recommended, selective agonists include CCPA (for A1AR of rat and mouse), CGS-21680 (for A2A AR of rat), and Cl-IB-MECA (for A3AR of all three species). The functionally selective partial A2B agonist BAY60-6583 was found to additionally bind to A1 and A3AR and act as an antagonist at both receptor subtypes. The antagonists PSB-36 (A1), preladenant (A2A), and PSB-603 (A2B) displayed high selectivity in all three investigated species. MRS-1523 acts as a selective A3AR antagonist in human and rat, but is only moderately selective in mouse. The comprehensive data presented herein provide a solid basis for selecting suitable AR ligands for biological studies.

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References

  1. Burnstock G (2012) Purinergic signalling: Its unpopular beginning, its acceptance and its exciting future. Bioessays 34:218–225

    Article  CAS  PubMed  Google Scholar 

  2. Burnstock G, Verkhratsky A (2009) Evolutionary origins of the purinergic signaling system. Acta Physiol (Oxf) 195:415–447

    Article  CAS  Google Scholar 

  3. Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552

    CAS  PubMed  Google Scholar 

  4. Jacobson KA, Balasubramanian R, Deflorian F, Gao ZG (2012) G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal 8:419–436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Müller CE, Jacobson KJ (2011) Xanthines as adenosine receptor antagonists. Handb Exp Pharmacol 200:151–199

    Article  PubMed  Google Scholar 

  6. Müller CE, Jacobson KA (2011) Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta 1808:1290–1308

    Article  PubMed Central  PubMed  Google Scholar 

  7. Heisig F, Gollos S, Freudenthal SJ, El-Tayeb A, Iqbal J, Müller CE (2014) Synthesis of BODIPY derivatives substituted with various bioconjugatable linker groups: a construction kit for fluorescent labeling of receptor ligands. J Fluoresc 24:213–230

    Article  CAS  PubMed  Google Scholar 

  8. Stoddart LA, Vernall AJ, Denman JL, Briddon SJ, Kellam B, Hill SJ (2012) Fragment screening at adenosine-A(3) receptors in living cells using a fluorescence-based binding assay. Chem Biol 19:1105–1115

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Kozma E, Jayasekara PS, Squarcialupi L, Paoletta S, Moro S, Federico S, Spalluto G, Jacobson KA (2013) Fluorescent ligands for adenosine receptors. Bioorg Med Chem Lett 23:26–36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, Cherezov V, Stevens RC (2011) Structure of an agonist-bound human A2A adenosine receptor. Science 332:322–327

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, Ijzerman AP, Stevens RC (2008) The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322:1211–1217

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Liu W, Chun E, Thompson AA, Chubukov P, Xu F, Katritch V, Han GW, Roth CB, Heitman LH, IJzerman AP, Cherezov V, Stevens RC (2012) Structural basis for allosteric regulation of GPCRs by sodium ions. Science 337:232–236

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Doré AS, Robertson N, Errey JC, Ng I, Hollenstein K, Tehan B, Hurrell E, Bennett K, Congreve M, Magnani F, Tate CG, Weir M, Marshall FH (2011) Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure 19:1283–1293

    Article  PubMed Central  PubMed  Google Scholar 

  14. de Lera RM, Lim YH, Zheng J (2014) Adenosine A2A receptor as a drug discovery target. J Med Chem 57:3623–3650

    Article  Google Scholar 

  15. Chen JF, Eltzschig HK, Fredholm BB (2013) Adenosine receptors as drug targets-what are the challenges? Nat Rev Drug Discov 12:265–286

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Albrecht-Küpper BE, Leineweber K, Nell PG (2012) Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal 8:91–99

    Article  PubMed Central  PubMed  Google Scholar 

  17. Liao Y, Lin L, Lu D, Fu Y, Bin J, Xu D, Kitakaze M (2011) Activation of adenosine A1 receptor attenuates tumor necrosis factor-α induced hypertrophy of cardiomyocytes. Biomed Pharmacother 65:491–495

    Article  CAS  PubMed  Google Scholar 

  18. Faulhaber-Walter R, Jou W, Mizel D, Li L, Zhang J, Kim SM, Huang Y, Chen M, Briggs JP, Gavrilova O, Schnermann JB (2011) Impaired glucose tolerance in the absence of adenosine A1 receptor signaling. Diabetes 60:2578–2587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Teerlink JR, Iragui VJ, Mohr JP, Carson PE, Hauptman PJ, Lovett DH, Miller AB, Piña IL, Thomson S, Varosy PD, Zile MR, Cleland JG, Givertz MM, Metra M, Ponikowski P, Voors AA, Davison BA, Cotter G, Wolko D, Delucca P, Salerno CM, Mansoor GA, Dittrich H, O’Connor CM, Massie BM (2012) The safety of an adenosine A(1)-receptor antagonist, rolofylline, in patients with acute heart failure and renal impairment: findings from PROTECT. Drug Saf 35:233–244

    Article  CAS  PubMed  Google Scholar 

  20. Nair PK, Marroquin OC, Mulukutla SR, Khandhar S, Gulati V, Schindler JT, Lee JS (2011) Clinical utility of regadenoson for assessing fractional flow reserve. JACC Cardiovasc Interv 4:1085–1092

    Article  PubMed  Google Scholar 

  21. Cheng AS, Pegg TJ, Karamitsos TD, Searle N, Jerosch-Herold M, Choudhury RP, Banning AP, Neubauer S, Robson MD, Selvanayagam JB (2007) Cardiovascular magnetic resonance perfusion imaging at 3-tesla for the detection of coronary artery disease: a comparison with 1.5-tesla. J Am Coll Cardiol 49:2440–2449

    Article  PubMed  Google Scholar 

  22. Lappas CM, Rieger JM, Linden J (2005) A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J Immunol 174:1073–1080

    Article  CAS  PubMed  Google Scholar 

  23. Haskó G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabó C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2A receptor-dependent and independent mechanisms. FASEB J 14:2065–2074

    Article  PubMed  Google Scholar 

  24. Flögel U, Burghoff S, van Lent PL, Temme S, Galbarz L, Ding Z, El-Tayeb A, Huels S, Bönner F, Borg N, Jacoby C, Müller CE, van den Berg WB, Schrader J (2012) Selective activation of adenosine A2A receptors on immune cells by a CD73-dependent prodrug suppresses joint inflammation in experimental rheumatoid arthritis. Sci Transl Med 4:146ra108

    PubMed  Google Scholar 

  25. Armentero MT, Pinna A, Ferré S, Lanciego JL, Müller CE, Franco R (2011) Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson’s disease. Pharmacol Ther 132:280–299

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Salamone JD, Collins-Praino LE, Pardo M, Podurgiel SJ, Baqi Y, Müller CE, Schwarzschild MA, Correa M (2013) Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: studies with a mouse model of parkinsonian tremor. Eur Neuropsychopharmacol 23:972–977

    Article  CAS  PubMed  Google Scholar 

  27. Jerónimo-Santos A, Batalha VL, Müller CE, Baqi Y, Sebastião AM, Lopes LV, Diógenes MJ (2014) Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP. Neuropharmacology 83:99–106

    Article  PubMed  Google Scholar 

  28. Jenner P (2005) Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson’s disease. Expert Opin Investig Drugs 14:729–738

    Article  CAS  PubMed  Google Scholar 

  29. Dungo R, Deeks ED (2013) Istradefylline: first global approval. Drugs 73:875–882

    Article  CAS  PubMed  Google Scholar 

  30. Koupenova M, Johnston-Cox H, Vezeridis A, Gavras H, Yang D, Zannis V, Ravid K (2012) A2B adenosine receptor regulates hyperlipidemia and atherosclerosis. Circulation 125:354–363

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Michael S, Warstat C, Michel F, Yan L, Müller CE, Nieber K (2010) Adenosine A(2A) agonist and A(2B) antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation. Purinergic Signal 6:117–124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Figler RA et al (2011) Links between insulin resistance, adenosine receptors and inflammatory markers in mice and humans. Diabetes 60:669–679

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Haskó G, Csóka B, Németh ZH, Vizi ES, Pacher P (2009) A2B adenosine receptors in immunity and inflammation. Trends Immunol 30:263–270

    Article  PubMed Central  PubMed  Google Scholar 

  34. Xiang HJ, Chai FL, Wang DS, Dou KF (2011) Downregulation of the adenosine a2b receptor by RNA interference inhibits hepatocellular carcinoma cell growth. ISNR Oncol 2011:875684–875687

    Google Scholar 

  35. Cekic C, Sag D, Li Y, Theodorescu D, Strieter RM, Linden J (2012) Adenosine A2B receptor blockade slows growth of baldder and breast tumors. J Immunol 188:198–205

    Article  CAS  PubMed  Google Scholar 

  36. Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, RosnerI RM, Mader R, Adawi M, Caspi D, Tishler M, Langevitz P, Rubinow A, Friedman J, Green L, Tanay A, Ochaion A, Cohen S, Kerns WD, Cohn I, Fishman-Furman S, Farbstein M, Yehuda SB, Fishman P (2008) Clinical evidence for the utilization of A3 adenosine receptor as a target to treat rheumatoid arthritis: data from phase II clinical trial. J Rheumatol 35:41–48

    CAS  PubMed  Google Scholar 

  37. Koscsó B, Csóka B, Pacher P, Haskó G (2011) Investigational A3 adenosine receptor targeting agents. Expert Opin Investig Drugs 20:757–768

    Article  PubMed Central  PubMed  Google Scholar 

  38. Wang Z, Do CW, Avila MY, Peterson-Yantorno K, Stone RA, Gao ZG, Joshi B, Besada P, Jeong LS, Jacobson KA, Civan MM (2010) Nucleosine-derived antagonists to A3 adenosine receptors lower mouse intraocular pressure and act across species. Exp Eye Res 90:146–154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Müller CE, Scior T (1993) Adenosine receptors and their modulators. Pharm Acta Helv 68:77–111

    Article  PubMed  Google Scholar 

  40. Auchampach JA, Kreckler LM, Wan TC, Maas JE, van der Hoeven D, Gizewski E, Narayanan J, Maas GE (2009) Characterization of the A2Badenosinereceptor from mouse, rabbit, and dog. J Pharmacol Exp Ther 329:2–13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Müller CE, Stein B (1996) Adenosine receptor antagonists: Structure and potential therapeutic applications. Curr Pharmaceut Design 2:501–530

    Google Scholar 

  42. X-d J, von Lubitz D, Olah ME, Stiles GL, Jacobson KA (1994) Species differences in ligands affinity at central A3 adenosine receptors. Drug Develop Res 33:51–59

    Article  Google Scholar 

  43. Weyler S, Fülle F, Diekmann M, Schumacher B, Hinz S, Klotz KN, Müller CE (2006) Improving potency, selectivity, and water solubility of adenosine A1 receptor antagonists: xanthines modified at position 3 and related pyrimido[1,2,3-cd] purinediones. Chem Med Chem 1:891–902

    Article  CAS  PubMed  Google Scholar 

  44. Yan L, Bertarelli DC, Hayallah AM, Meyer H, Klotz KN, Müller CE (2006) A new synthesis of sulfonamides by aminolysis of p-nitrophenylsulfonates yielding potent and selective adenosine A2B receptor antagonists. J Med Chem 49:4384–4391

    Article  CAS  PubMed  Google Scholar 

  45. Müller CE, Shi D, Manning M Jr, Daly JW (1993) Synthesis of paraxanthine analogs (1,7-disubstituted xanthines) and other xanthinesunsubstituted at the 3-position: structure-activity relationships at adenosine receptors. J Med Chem 36:3341–3349

    Article  PubMed  Google Scholar 

  46. Borrmann T, Hinz S, Bertarelli DC, Li W, Florin NC, Scheiff AB, Müller CE (2009) 1-alkyl-8-(piperazine-1-sulfonyl) phenylxanthines: development and characterization of adenosineA2B receptor antagonists and a new radioligand with subnanomolar affinity and subtype specificity. J Med Chem 52:3994–400

    Article  CAS  PubMed  Google Scholar 

  47. Hockemeyer J, Burbiel JC, Müller CE (2004) Multigram-scale syntheses, stability, and photoreactions of A2A adenosine receptor antagonists with 8-styrylxanthine structure: Potential drugs for Parkinson’s disease. J Org Chem 69:3308–3318

    Article  CAS  PubMed  Google Scholar 

  48. Neustadt BR, Hao J, Lindo N, Greenlee WJ, Stamford AW, Tulshian D, Ongini E, Hunter J, Monopoli A, Bertorelli R, Foster C, Arik L, Lachowicz J, Ng K, Feng KI (2007) Potent, selective, and orally active adenosine A2A receptor antagonists: Arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidines. Bioorg Med Chem Lett 5:1376–1380

    Article  Google Scholar 

  49. Klotz KN, 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 357:1–9

    Article  CAS  PubMed  Google Scholar 

  50. Klotz KN, Lohse MJ, Schwabe U, Cristalli G, Vittori S, Grifantini M (1989) 2-Chloro-N6-[3H] cyclopentyladenosine ([3H]CCPA)- a high affinity agonist radioligand for A1 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 340:679–683

    Article  CAS  PubMed  Google Scholar 

  51. Schumacher B (2002) Identifizierung, Struktur-Wirkungsbeziehungen und Aktivitätsprofile neuer Adenosinrezeptor-Liganden, University of Bonn

  52. Reith U (2001) Native und rekombinante humane Adenosinrezeptoren: Charakterizierung, Interaktion mit pflanzlichen Inhaltsstoffen und Suche nach neuen Leitstrukturen, University of Bonn

  53. Sihver W, Schulze A, Wutz W, Stüsgen S, Olsson RA, Bier D, Holschbach MH (2009) Autoradiographiccomparison of in vitro binding characteristics of various tritiated adenosine A2A receptor ligands in rat, mouse and pig brain and first ex vivo results. Eur J Pharmacol 616:107–114

    Article  CAS  PubMed  Google Scholar 

  54. Daly JW, Padgett WL, Secunda SI, Thompson RD, Olsson RA (1993) Structure-activity relationships for 2-substituted adenosines at A1 and A2 adenosine receptors. Pharmacology 46:91–100

    Article  CAS  PubMed  Google Scholar 

  55. Vittori S, Lorenzen A, Stannek C, Costanzi S, Volpini R, IJzerman AP, Kunzel JK, Cristalli G (2000) N-cycloalkyl derivatives of adenosine and 1-deazaadenosine as agonists and partial agonists of the A(1) adenosine receptor. J Med Chem 43:250–260

    Article  CAS  PubMed  Google Scholar 

  56. Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE (2011) International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors-an update. Pharmacol Rev 63:1–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Tchilibon S, Joshi BV, Kim SK, Duong HT, Gao ZG, Jacobson KA (2005) (N)-methanocarba 2,N6-disubstituted adenine nucleosides as highly potent and selective A3 adenosine receptor agonists. J Med Chem 6:1745–1758

    Article  Google Scholar 

  58. Müller CE (2001) adenosine receptor ligands-recent developments part I. Agonists. Curr Med Chem 7:1269–1288

    Article  Google Scholar 

  59. Jacobson KA (1998) Adenosine A3 receptors: Novel ligands and paradoxical effects. Trends Pharmacol Sci 5:184–191

    Article  Google Scholar 

  60. Abo-Salem OM, Hayallah AM, Bilkei-Gorzo A, Filipek B, Zimmer A, Müller CE (2004) Antinociceptive effects of novel A2B adenosine receptor antagonists. J Pharmacol Exp Ther 1:358–366

    Google Scholar 

  61. Kenneth AK, Ijzerman AP, Linden J (1999) 1,3-dialkylxanthine derivatives having high potency as antagonists at human A2B adenosine receptors. Drug Devel Res 47:45–53

    Article  Google Scholar 

  62. Grahner B, Winiwarter S, Lanzner W, Müller CE (1994) Synthesis and structure-activity relationships of deazaxanthines: Analogs of potent A1- and A2-adenosine receptor antagonists. J Med Chem 37:1526–1534

    Article  CAS  PubMed  Google Scholar 

  63. Bulicz J, Bertarelli DC, Baumert D, Fülle F, Müller CE, Heber D (2006) Synthesis and pharmacology of pyrido [2,3-d] pyrimidinediones bearing polar substituents as adenosine receptor antagonists. Bioorg Med Chem 14:2837–2849

    Article  CAS  PubMed  Google Scholar 

  64. Massip S, Guillon J, Bertarelli D, Bosc JJ, Léger JM, Lacher S, Bontemps C, Dupont T, Müller CE, Jarry C (2006) Synthesis and preliminary evaluation of new 1- and 3-[1-(2-hydroxy-3-phenoxypropyl)] xanthines from 2-amino-2-oxazolines as potential A1 and A2A adenosine receptor antagonists. Bioorg Med Chem 14:2697–2719

    Article  CAS  PubMed  Google Scholar 

  65. Klotz KN, Vogt H, Tawfik-Schlieper H (1991) Comparison of A1 adenosine receptors in brain from different species by radioligand binding and photoaffinity labelling. Naunyn Schmiedebergs Arch Pharmacol 343:196–201

    Article  CAS  PubMed  Google Scholar 

  66. Kieć-Kononowicz K, Drabczyńska A, Pękala E, Michalak B, Müller CE, Schumacher B, Karolak-Wojciechowska J, Duddeck H, Rockitt S, Wartchow R (2001) New developments in A1 and A2A adenosine receptor antagonists. Pure Appl Chem 73:1411–1420

    Google Scholar 

  67. Kim YC, Ji X, Melman N, Linden J, Jacobson KA (2000) Anilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A(2B) adenosine receptors. J Med Chem 43:1165–1172

    Article  CAS  PubMed  Google Scholar 

  68. Akkari R, Burbiel JC, Hockemeyer J, Müller CE (2006) Recent progress in the development of adenosine receptor ligands as antiinflammartory drugs. Curr Top Med Chem 6:1375–1379

    Article  CAS  PubMed  Google Scholar 

  69. Gao ZG, Blaustein JB, Gross AS, Melman N, Jacobson KA (2003) N6-Substituted adenosine derivatives: selectivity, efficacy, and species differences at A3 adenosine receptors. Biochem Pharmacol 65:1675–1684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Müller CE (2001) A3 adenosine receptor antagonsits. Mini Rev Med Chem 1:417–427

    Article  PubMed  Google Scholar 

  71. Olson KR, Eglen RM (2007) Beta-galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol 5:137–144

    Article  CAS  PubMed  Google Scholar 

  72. Müller CE, Maurinsh J, Sauer R (2000) Binding of [3H]MSX-2 (3-(3-hydroxypropyl)-7-methyl-8-(m-methoxystyryl)-1-propargylxanthine) to rat striatal membranes—a new, selective antagonist radioligand for A(2A) adenosine receptors. Eur J Pharm Sci 10:259–265

    Article  PubMed  Google Scholar 

  73. Bertarelli DC, Diekmann M, Hayallah AM, Rüsing D, Iqbal J, Preiss B, Verspohl EJ, Müller CE (2006) Characterization of human and rodent native and recombinant adenosine A(2B) receptors by radioligand binding studies. Purinergic Signal 2:559–571

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Seibt BF, Schiedel AC, Thimm D, Hinz S, Sherbiny FF, Müller CE (2013) The second extracellular loop of GPCRs determines subtype-selectivity and controls efficacy as evidenced by loop exchange study at A2 adenosine receptors. Biochem Pharmacol 85:1317–1329

    Article  CAS  PubMed  Google Scholar 

  75. Kim SA, Marshall MA, Melman N, Kim HS, Müller CE, Linden J, Jacobson KA (2002) Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions. J Med Chem 45:2131–2138

    Article  CAS  PubMed  Google Scholar 

  76. Bruns RF, Lu GH, Pugsley TA (1986) Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol 29:331–346

    CAS  PubMed  Google Scholar 

  77. Hayallah AM, Sandoval-Ramírez J, Reith U, Schobert U, Preiss B, Schumacher B, Daly JW, Müller CE (2002) 1,8-disubstituted xanthine derivatives: Synthesis of potent A2B-selective adenosine receptor antagonists. J Med Chem 45:1500–1510

    Article  CAS  PubMed  Google Scholar 

  78. Müller CE, Diekmann M, Thorand M, Ozola V (2002) [(3)H]8-Ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo [2,1-i]-purin-5-one ([(3)H]PSB-11), a novel high-affinity antagonist radioligand for human A(3) adenosine receptors. Bioorg Med Chem Lett 12:501–503

    Article  PubMed  Google Scholar 

  79. Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG (1993) Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci U S A 90:10365–10369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. van Galen PJ, van Bergen AH, Gallo-Rodriguez C, Melman N, Olah ME, IJzerman AP, Stiles GL, Jacobson KA (1994) A binding site model and structure-activity relationships for the rat A3 adenosine receptor. Mol Pharmacol 45:1101–1111

    PubMed  Google Scholar 

  81. Rosentreter U, Henning R, Bauser M, Krämer T, Vaupel A, Hübsch W, Dembowsky K, Salcher-Schraufstätter O, Stasch J P, Krahn T, Perzborn E (2006) Substituted 2-thio-3,5-dicyano-4-aryl-6-aminopyridines and the use thereof. 1–273

  82. van der Hoeven D, Wan TC, Gizewski ET, Kreckler LM, Maas JE, Van Orman J, Ravid K, Auchampach JA (2011) A role for the low-affinity A2B adenosine receptor in regulating superoxide generation by murine neutrophils. J Pharmacol Exp Ther 338:1004–1012

    Article  PubMed Central  PubMed  Google Scholar 

  83. Hinz S, Lacher SK, Seibt BF, Müller CE (2014) BAY60-6583 acts as a partial agonist at adenosine A2B receptors. J Pharmacol Exp Ther 349:427–436

    Article  PubMed  Google Scholar 

  84. Jacobson KA (2013) Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates. J Med Chem 56:3749–3767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Murphree LJ, Marshall MA, Rieger JM, MacDonald TL, Linden J (2002) Human A(2A) adenosine receptors: High-affinity agonist binding to receptor-G protein complexes containing Gbeta(4). Mol Pharmacol 61:455–462

    Article  CAS  PubMed  Google Scholar 

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  1. Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121, Bonn, Germany

    Mohamad Wessam Alnouri, Stephan Jepards, Alessandro Casari, Anke C. Schiedel, Sonja Hinz & Christa E. Müller

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  1. Mohamad Wessam Alnouri
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Alnouri, M.W., Jepards, S., Casari, A. et al. Selectivity is species-dependent: Characterization of standard agonists and antagonists at human, rat, and mouse adenosine receptors. Purinergic Signalling 11, 389–407 (2015). https://doi.org/10.1007/s11302-015-9460-9

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