Abstract
Neurochemical and pharmcological evidence obtained over the past 300 yr has indicated that adenosine and dopamine interact functionally in the basal ganglia and that such interactions have pathophysiological and theraputic implications. The receptors implicated are adenosine A1 and A2A, and dopamine D1 and D2. There is evidence that dopamine D2 receptor activation in vivo antagonizes tonic activation of adenosine A2A receptors. Thus, acute blockade of dopamine D2 receptors, or disruption of dopamine transmission, unmasks strong adenosine A2A activation. Effects of dopamine D2 blockade are different after adenosine A2A blockade or in A2A knockout mice. Possibly as an adaptation to this increase in adenosine A2A signaling, there is a decreased coupling of A2A receptors to biological effects in dopamine D2 knockout mice. Compared to wild-type mice, adenosine A2A knockout mice show decreased neurodegeneration after treatment with 1-myeyl-1,2,3,6-tetrahydropyridine (MPTP) and show improved motor performance in models of Parkinson’s disease Adenosine A1 receptors are not spccifically located with any dopamine receptor, as is the A2A receptor with D2 receptors. Many A1 receptors are located presynaptically, where they regulate transmitter release. In A1 knockout mice, glutamatergic and dopaminergic transmission is therefore modified.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Calabresi P., Centonze D., Pisani A., and Bernardi G. (1997) Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses. J. Neurosci. 17, 4509–4516.
Chen J. F. (2003) The adenosine A(2A) receptor as an attractive target for Parkinson’s disease treatment. Durg News Perspect. 16, 597–604.
Chen J. F., Moratalla R., Impagnatiello F., Grandy D. K., Cuellar B., Rubinstein M., et al. (2001a) The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc. Natl. Acad. Sci. U. S. A. 98, 1970–1975.
Chen J. F., Xu K., Petzer J. P., Staal R., Xu Y. H., Beilstein M., et al. (2001b) Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease. J. Neurosci. 21, RC143.
Corvol J. C., Studler J. M., Schonn J. S., Girault J. A., and Herve D. (2001) Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J. Neurochem. 76, 1585–1588.
Dunwiddie T. V. and Masino S. A. (2001) The role and regulation of adenosine in the central nervous system. Annu. Rev. Neurosci. 24, 31–55.
El Yacoubi M., Ledent C., Menard J. F., Parmentier M., Costentin J., and Vaugeois J. M. (2000) The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A(2A) receptors. Br. J. Pharmacol. 129, 1465–1473.
El Yacoubi M., Ledent C., Parmentier M., Costentin J., and Vaugeois J. M. (2001) Adenosine A2A receptor knockout mice are partially protected against drug-induced catalepsy. Neuroreport 12, 983–986.
Ferré S., Fredholm B. B., Morelli M., Popoli P., and Fuxe K. (1997) Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci. 20, 482–487.
Ferré S., von Euler G., Johansson B., Fredholm B. B., and Fuxe K. (1991) Stimulation of high-affinity adenosine A2 receptors decreases and affinity of dopamine D2 receptors in rat striatal membranes. Proc. Natl. Acad. Sci. U. S. A. 88, 7238–7241.
Flagmeyer I., Haas H. L., and Stevens D. R. (1997) Adenosine A1 receptor-mediated depression of corticostriatal and thalamostriatal glutamatergic synaptic potentials in vitro. Brain Res. 778, 178–185.
Fredholm B. B. and Dunwiddie T. V. (1988) How does adenosine inhibit transmitter release? Trends Pharmacol. Sci. 9, 130–134.
Fredholm B. B. and Svenningsson P. (2003) Adenosine-dopamine interactions: development of a concept and some comments on therapeutic possibilities. Neurology 61(Suppl. 6), S5-S9.
Fredholm B. B., Bättig K., Holmén J., Nehlig A., and Zvartau E. (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol. Rev. 51, 83–153.
Fredholm B. B., Cunha R., and Svenningsson P. (2003) Pharmacology of adenosine A2A receptors and therapeutic applications. Curr. Top. Med. Chem. 3, 413–426.
Fuxe K. and Ungerstedt U. (1974) Action of caffeine and theophyllamine on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with DOPA and dopamine receptor agonists. Med. Biol. 52, 48–54.
Fuxe K., Strömberg I., Popoli P., Rimondini-Giorgini R., Torvinen M., Ogren S. O., et al. (2001) Adenosine receptors and Parkinson’s disease. Relevance of antagonistic adenosine and dopamine receptor interactions in the striatum. Adv. Neurol. 86, 345–353.
Glatt C. E. and Snyders S. H. (1993) Cloning and expression of an adenylyl cyclase localized to the corpus striatum. Nature 361, 536–538.
Halldner L., Ådén U., Dahlberg V., Johansson B., Ledent C., and Fredholm B. B. (2004) The adenosine A1 receptor contributes to the stimulatory, but not the inhibitory effect of caffeine on locomotion: a study in mice lacking adenosine A1 and/or A2A receptors. Neuropharmacology 46, 1008–1017.
Hervé D., Le Moine C., Corvol J. C., Belluscio L., Ledent C., Fienberg A. A., et al. (2001) Galpha(olf) levels are regulated by receptor usage and control dopamine and adenosine action in the striatum. J. Neurosci. 21, 4390–4399.
Jones D. T., Masters S. B., Bourne H. R., and Reed R. R. (1990) Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf. J. Biol. Chem. 265, 2671–2676.
Kim D. S. and Palmiter R. D. (2003) Adenosine receptor blockade reverses hypophagia and enhances locomotor activity of dopamine-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 100, 1346–1351.
Kull B., Svenningsson P., and Fredholm B. B. (2000) Adenosine A2A receptors are co-localized with and activate Golf in rat striatum. Mol. Pharmacol. 58, 771–777.
Lee K. W., Hong J. H., Choi I. Y., Che Y., Lee J. K., Yang S. D., et al. (2002) Imparied D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. J. Neurosci. 22, 7931–7940.
Lindskog M., Svenningsson P., Pozzi L., Kim Y., Fienberg A. A., Bibb J. A., et al. (2002) Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Nature 418, 774–778.
Masino S. A., Diao L., Illes P., Zahniser N. R., Larson G. A., Johansson B., et al. (2002) Modulation of hippocampal glutamatergic transmission by ATP is dependent on adenosine A1 receptors. J. Pharmacol. Exp. Ther. 303, 356–363.
Moore K. A., Nicoll R. A., and Schmitz D. (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses. Proc. Natl. Acad. Sci. U. S. A. 100, 14397–14402.
Scammell T. E., Arrigoni E., Thompson M. A., Ronan P. J., Saper C. B., and Greene R. W. (2003) Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector. J. Neurosci. 23, 5762–5770.
Solinas M., Ferré S., You Z. B., Karcz-Kubicha M., Popoli P., and Goldberg S. R. (2002) Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J. Neurosci. 22, 6321–6324.
Svenningsson P., Fourreau L., Bloch B., Fredholm B. B., Gonon F., and Le Moine C. (1999a) Opposite tonic modulation of dopamine and adenosine on c-fos mRNA expression in striatopallidal neurons. Neuroscience 89, 827–837.
Svenningsson P., Le Moine C., Fisone G., and Fredholm B. B. (1999a) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog. Neurobiol. 59, 355–396.
Svenningsson P., Lindskog M., Ledent C., Parmentier M., Greengard P., Fredholm B. B., and Fisone G. (2002) Regulation of the phosphorylation of the dopamine-and cAMP-regulated phosphoprotein of 32 kDa in viro by dopamine D1, dopamine D2 and adenosine A2A receptors. Proc. Natl. Acad. Sci. U. S. A. 97, 1856–1860.
Svenningsson P., Lindskog M., Rognoni F., Fredholm B. B., Greengard P., and Fisone G. (1998) Activation of adenosine A2A and dopamine D1 receptors stimulates cyclic AMP-dependent phosphorylation of DARPP-32 in distinct populations of striatal projection neurons. Neuroscience 84, 223–228.
Svenningsson P., Nomikos G. G., Ongini E., and Fredholm B. B. (1997) Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate-putamen and nucleus accumbens. Neuroscience 79, 753–764.
Zahniser N. R., Simosky J. K., Mayfield R. D., Negri C. A., Hanania T., Larson G. A., et al. (2000) Functional uncoupling of adenosine A2A receptors and reduced response to caffeine in mice lacking dopamine D2 receptors. J. Neurosci. 20, 5949–5957.