Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Eur Neuropsychopharmacol. 2015 Sep;25(9):1462-9. doi: 10.1016/j.euroneuro.2014.11.021. Epub 2014 Dec 9.
Novel structural and functional aspects of the dopamine (DA) D3 receptors (D3R) have been recently described. D3R expressed in dopaminergic neurons have been classically considered to play the role of autoreceptors inhibiting, as the D2R, DA release. However, evidence for D3R-mediated neurotrophic and neuroprotective effects on DA neurons suggests their involvement in preventing pathological alterations leading to neurodegeneration. On the other hand, given its localization and functional role at postsynaptic striatal levels, the D3R may also be involved in the pathogenesis of movement disorders and psychiatric diseases. Functional interactions of D3R with other receptor systems are crucial for the modulation of several physiological events. On this line, the discovery that the D3R can form heteromers with other receptors has opened the possibility of uncover novel molecular mechanisms of brain functions and dysfunctions. This paper summarizes the functional and physical interactions of D3R with other receptors both at pre-synaptic sites, where it is co-expressed with the D2R and nicotinic receptors, and at post-synaptic sites where it interacts with the DA D1 receptors (D1R). The biochemical and functional properties of the D1R-D3R heteromer will be especially discussed. Both D1R and D3R have been in fact implicated in several disorders, including schizophrenia and motor dysfunctions. Therefore, the D1R-D3R heteromer may represent a potential drug target for the treatment of these diseases.
最近描述了多巴胺 (DA) D3 受体 (D3R) 的新结构和功能方面。在多巴胺能神经元中表达的 D3R 经典地被认为具有作为自身受体的作用，抑制 DA 的释放，就像 D2R 一样。然而，D3R 介导的对 DA 神经元的神经营养和神经保护作用的证据表明，它们参与预防导致神经退行性变的病理改变。另一方面，鉴于其在纹状体突触后水平的定位和功能作用，D3R 也可能参与运动障碍和精神疾病的发病机制。D3R 与其他受体系统的功能相互作用对于调节几种生理事件至关重要。在这方面，发现 D3R 可以与其他受体形成异源二聚体，这为揭示大脑功能和功能障碍的新分子机制开辟了可能性。本文总结了 D3R 与其他受体在突触前部位（与 D2R 和烟碱受体共表达）和突触后部位（与 DA D1 受体（D1R）相互作用）的功能和物理相互作用。将特别讨论 D1R-D3R 异源二聚体的生化和功能特性。事实上，D1R 和 D3R 都与几种疾病有关，包括精神分裂症和运动功能障碍。因此，D1R-D3R 异源二聚体可能是治疗这些疾病的潜在药物靶点。
