Experimental Evidence of A 2A -D 2 Receptor-Receptor Interactions in the Rat and Human Carotid Body

• Published in: Frontiers in physiology 2021, Vol.12, p.645723
• Main Authors: Stocco, Elena, Sfriso, Maria Martina, Borile, Giulia, Contran, Martina, Barbon, Silvia, Romanato, Filippo, Macchi, Veronica, Guidolin, Diego, De Caro, Raffaele, Porzionato, Andrea
• Format: Article
• Language: English
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2021.645723

Adenosine A receptors (A R) and dopamine D receptors (D R) 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, A R and D R 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 A R and D R 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 A R-D R heterodimers by proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase/S100 colocalization indicated the formation of A R-D R heterodimers in type I and II cells of the CB; the presence of A R-D R 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.