Human ADORA1

Figure. Concentration-dependent activation of ADORA1 by NECA

Reporter cells were transfected with either the expression plasmid for human adenosine A1 receptor (ADORA1) or the mock plasmid and treated with various concentrations of NECA. Data points shown are the mean ± SEM of an experiment (n = 3), and the curve is a fit to Hill equation with an EC50 of 4.8 nM.

adenosine A1 receptor
Available assay modes
Agonist, Inverse agonist, Antagonist, PAM, NAM
à la carte, Neurology, Cardiology, Respiratory, Human non-orphan GPCRs

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

Related Receptors

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