Adenosine Receptors as a Paradigm to Identify Dimer/Oligomers of G-Protein-Coupled Receptors and as Targets in Parkinson’s Disease and Schizophrenia

Abstract

While adrenergic receptors were instrumental to start to understand the role of GPCRs, other receptors are taking the lead to understand why GPCR homo−/heteromers are needed and to address their physiological consequences in both healthy/homeostatic conditions and disease. Adenosine and dopamine receptors in the CNS are instrumental to understand pathogenic mechanisms in Parkinson’s disease and to know the role of receptor heteromers. We here provide the account of the heteroreceptor complexes formed by adenosine receptors (A1, A2A, A2B, and A3), and their potential as therapeutic targets. Both adenosine (A1 or A2A)-dopamine (D1 or D2) and adenosine A1A2A heteroreceptor complexes are therapeutic targets in Parkinson’s disease and may be altered after chronic levodopa treatment. A short account on the potential of adenosine receptors as targets in schizophrenia is also provided. Apart from potential in combating symptoms, adenosine receptors have potential as targets for neuroprotection. However, the design of neuroprotective drugs requires to understand how adenosine affects microglia and which adenosine-receptor-containing heteromers may be targeted.