title: Adenosine A2A-D2 receptor-receptor interactions in putative heteromers in the regulation of the striato-pallidal gaba pathway: possible relevance for parkinson's disease and its treatment.
abstract: Striatal dopamine adenosine A2A and D2 receptors interact to modulate some aspects of motor and motivational function. The demonstration of A2A/D2 receptor heteromerization in living cells constituted a progress for understanding the neurobiology of dopamine D2 and adenosine A2A receptors. In fact, the existence of putative striatalA2A/D2 receptor heteromers has been suggested to be important for striatal function under both normal and pathological conditions, such as Parkinson's disease. Consequently, the antagonistic A2A-D2 receptor interactions in a putative striatal receptor heteromer on striato-pallidal GABA neuron led to the introduction of A2A receptor antagonists as possible anti- Parkinsonian drugs. The present mini-review briefly summarizes the main findings supporting the presence of antagonistic A2A-D2 receptor interactions in putative receptor heteromers in the basal ganglia. Special emphasis is given to in vivo microdialysis findings demonstrating the functional role putative A2A/D2 heteromers on striato-pallidal GABA neurons play in the modulation of this pathway, in which A2A receptors inhibit D2 receptor signaling. The possible relevance of compounds targeting the putative striatal A2A/D2 heteromer in the Parkinson's disease pharmacological treatment is also discussed.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beggiato
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
authors.forename: Maria C
authors.initials: MC
authors.lastname: Tomasini
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Borelli
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Sergio
authors.initials: S
authors.lastname: Tanganelli
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy. tgs@unife.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D055503:Protein Multimerization; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid