AUTHOR=Stocco Elena , Sfriso Maria Martina , Borile Giulia , Contran Martina , Barbon Silvia , Romanato Filippo , Macchi Veronica , Guidolin Diego , De Caro Raffaele , Porzionato Andrea 

TITLE=Experimental Evidence of A2A–D2 Receptor–Receptor Interactions in the Rat and Human Carotid Body

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.645723

DOI=10.3389/fphys.2021.645723

ISSN=1664-042X

ABSTRACT=<p>Adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>R) and dopamine D<sub>2</sub> receptors (D<sub>2</sub>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<sub>2A</sub>R and D<sub>2</sub>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<sub>2A</sub>R and D<sub>2</sub>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<sub>2A</sub>R–D<sub>2</sub>R heterodimers by <italic>in situ</italic> proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase/S100 colocalization indicated the formation of A<sub>2A</sub>R–D<sub>2</sub>R heterodimers in type I and II cells of the CB; the presence of A<sub>2A</sub>R–D<sub>2</sub>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.</p>