Stocco Elena, Sfriso Maria Martina, Borile Giulia, Contran Martina, Barbon Silvia, Romanato Filippo, Macchi Veronica, Guidolin Diego, De Caro Raffaele, Porzionato Andrea
Department of Neuroscience, Institute of Human Anatomy, University of Padova, Padua, Italy.
Department of Physics and Astronomy "G. Galilei," University of Padova, Padua, Italy.
Front Physiol. 2021 Apr 15;12:645723. doi: 10.3389/fphys.2021.645723. eCollection 2021.
Adenosine A receptors (AR) and dopamine D receptors (DR) are known to be involved in the physiological response to hypoxia, and their expression/activity may be modulated by chronic sustained or intermittent hypoxia. To date, AR and DR can form transient physical receptor-receptor interactions (RRIs) giving rise to a dynamic equilibrium able to influence ligand binding and signaling, as demonstrated in different native tissues and transfected mammalian cell systems. Given the presence of AR and DR in type I cells, type II cells, and afferent nerve terminals of the carotid body (CB), the aim of this work was to demonstrate here, for the first time, the existence of AR-DR heterodimers by proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase/S100 colocalization indicated the formation of AR-DR heterodimers in type I and II cells of the CB; the presence of AR-DR heterodimers also in afferent terminals is also suggested by PLA signal distribution. RRIs could play a role in CB dynamic modifications and plasticity in response to development/aging and environmental stimuli, including chronic intermittent/sustained hypoxia. Exploring other RRIs will allow for a broad comprehension of the regulative mechanisms these interactions preside over, with also possible clinical implications.
已知腺苷 A 受体（AR）和多巴胺 D 受体（DR）参与对缺氧的生理反应，并且它们的表达/活性可能受到慢性持续性或间歇性缺氧的调节。迄今为止，正如在不同的天然组织和转染的哺乳动物细胞系统中所证明的那样，AR 和 DR 可以形成瞬时的物理受体 - 受体相互作用（RRI），产生一种能够影响配体结合和信号传导的动态平衡。鉴于在颈动脉体（CB）的 I 型细胞、II 型细胞和传入神经末梢中存在 AR 和 DR，本研究的目的是首次通过邻近连接分析（PLA）证明 AR - DR 异二聚体的存在。我们通过 PLA 分析以及酪氨酸羟化酶/S100 共定位得到的数据表明，在 CB 的 I 型和 II 型细胞中形成了 AR - DR 异二聚体；PLA 信号分布也提示在传入神经末梢中也存在 AR - DR 异二聚体。RRI 可能在 CB 对发育/衰老和环境刺激（包括慢性间歇性/持续性缺氧）的动态修饰和可塑性中发挥作用。探索其他 RRI 将有助于广泛理解这些相互作用所主导的调节机制，也可能具有临床意义。
