Adenosine receptors


Adenosine receptors are activated by the endogenous ligand adenosine (potentially inosine also at A3 receptors). Crystal structures for the antagonist-bound [1,2,3,4], agonist-bound [5,6,7] and G protein-bound A2A adenosine receptors [8] have been described. The structures of an antagonist-bound A1 receptor [9] and an adenosine-bound A1 receptor-Gi complex [10] have been resolved by cryo-electronmicroscopy. Another structure of an antagonist-bound A1 receptor obtained with X-ray crystallography has also been reported [11]. caffeine is a nonselective antagonist for adenosine receptors, while istradefylline, a selective A2A receptor antagonist, is on the market for the treatment of Parkinson's disease.


  1. Jaakola VP, Griffith MT, Hanson MA, et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 2008;322:1211-7.
  2. Segala E, Guo D, Cheng RK, et al. Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength. J Med Chem 2016;59:6470-9.
  3. Liu W, Chun E, Thompson AA, et al. Structural basis for allosteric regulation of GPCRs by sodium ions. Science 2012;337:232-6.
  4. Congreve M, Andrews SP, Doré AS, et al. Discovery of 1,2,4-triazine derivatives as adenosine A(2A) antagonists using structure based drug design. J Med Chem 2012;55:1898-903.
  5. Xu F, Wu H, Katritch V, et al. Structure of an agonist-bound human A2A adenosine receptor. Science 2011;332:322-7.
  6. Lebon G, Edwards PC, Leslie AG, et al. Molecular Determinants of CGS21680 Binding to the Human Adenosine A2A Receptor. Mol Pharmacol 2015;87:907-15.
  7. Lebon G, Warne T, Edwards PC, et al. Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 2011;474:521-5.
  8. Carpenter B, Nehmé R, Warne T, et al. Structure of the adenosine A(2A) receptor bound to an engineered G protein. Nature 2016;536:104-7.
  9. Glukhova A, Thal DM, Nguyen AT, et al. Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity. Cell 2017;168:867-877.e13.
  10. Draper-Joyce CJ, Khoshouei M, Thal DM, et al. Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature 2018;558:559-563.
  11. Cheng RKY, Segala E, Robertson N, et al. Structures of Human A1 and A2A Adenosine Receptors with Xanthines Reveal Determinants of Selectivity. Structure 2017;25:1275-1285.e4.
Excerpt from IUPHAR/BPS Guide to Pharmacology
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