A2A Receptor

Connection Between A2A Receptor and Adenyl Cyclase


Adenosine is an important molecule in the human body. Extracellular adenosine has been linked to different functions involving the central nervous system (CNS) including pain regulation, blood flow, breathing and sleep. It does this through binding to G-protein coupled receptors (GPCR), one of which is termed A2A. This receptor is linked to Gs and Golf and upon activation, the intracellular levels of cAMP increase. cAMP is a common secondary messenger in the cell.[1]

In general terms of the Gs complex, the α subunit of this protein exchanges GDP for GTP. This allows for the
α subunit to break apart from the complex (which contains the β and γ subunits) and bind to adenyl cylase which turns ATP into cAMP as mentioned.[2] However, new research has shown that depending on the tissue type such as that found in the striatum, the favorability of Golf (typically linked with dopamine instead of adenine) over Gs is seen in terms of activating adenyl cylcase. [3]

The A2A receptor can also affect phosphodiesterase where desensitization of A2A along with increased cAMP leads to increased levels of phosphodiesterase.[4]


A2A_binding_.png
Figure 1. Important residues and their relative distance in angstroms away from an inhibitor, ZM241385, which is structurally similar to caffeine. Adapted from Jaakola, V., Griffith, M.T., Hanson, M.A., Cherezov, V., Chien, E.Y.T., Lane, R., Ijzerman, A.P., and Stevens, R.C. (2008) Science, 322, 1211-1217
Pathway 1
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Pathway 2
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  1. ^ Jaakola, V., Griffith, M.T., Hanson, M.A., Cherezov, V., Chien, E.Y.T., Lane, R., Ijzerman, A.P., and Stevens, R.C. (2008) Science. 322, 1211-1217
  2. ^ Hanoune, J.,and Defer, N., (2001) Toxicol. 41, 145-174
  3. ^ Kull, B., Svenningsson P., and Fredholm, B.B., (2000) Molecular Pharmacology. 58(4), 771-777
  4. ^ Chang, Y.H., Conti, M., Lee, Y.C., Lai, H.L., Ching, Y.H., and Chern Y. (2002) Journal of Neurochemistry. 69(3), 1300-1309