Beggiato Sarah, Antonelli Tiziana, Tomasini Maria C, Borelli Andrea C, Agnati Luigi F, Tanganelli Sergio, Fuxe Kjell, Ferraro Luca
Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy.
Curr Protein Pept Sci. 2014;15(7):673-80. doi: 10.2174/1389203715666140901103205.
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.
纹状体多巴胺、腺苷A2A和D2受体相互作用，调节运动和动机功能的某些方面。活细胞中A2A/D2受体异聚体的证明是理解多巴胺D2和腺苷A2A受体神经生物学的一个进展。事实上，推测纹状体A2A/D2受体异聚体的存在对于正常和病理条件下（如帕金森病）的纹状体功能很重要。因此，推测的纹状体受体异聚体中A2A-D2受体的拮抗相互作用导致了A2A受体拮抗剂作为可能的抗帕金森病药物的引入。本综述简要总结了支持基底神经节中推测的受体异聚体存在A2A-D2受体拮抗相互作用的主要发现。特别强调了体内微透析的发现，这些发现证明了推测的A2A/D2异聚体在纹状体苍白球GABA神经元上对该通路调节的功能作用，其中A2A受体抑制D2受体信号传导。还讨论了靶向推测的纹状体A2A/D2异聚体的化合物在帕金森病药物治疗中的可能相关性。
