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To date, A<jats:sub>2A<\/jats:sub>R and D<jats:sub>2<\/jats:sub>R can form transient physical receptor\u2013receptor 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<jats:sub>2A<\/jats:sub>R and D<jats:sub>2<\/jats: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<jats:sub>2A<\/jats:sub>R\u2013D<jats:sub>2<\/jats:sub>R heterodimers by <jats:italic>in situ<\/jats:italic> proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase\/S100 colocalization indicated the formation of A<jats:sub>2A<\/jats:sub>R\u2013D<jats:sub>2<\/jats:sub>R heterodimers in type I and II cells of the CB; the presence of A<jats:sub>2A<\/jats:sub>R\u2013D<jats:sub>2<\/jats: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.<\/jats:p>","DOI":"10.3389\/fphys.2021.645723","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T18:28:42Z","timestamp":1618511322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Experimental Evidence of A2A\u2013D2 Receptor\u2013Receptor Interactions in the Rat and Human Carotid Body"],"prefix":"10.3389","volume":"12","author":[{"given":"Elena","family":"Stocco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Martina","family":"Sfriso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Borile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Contran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Barbon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Romanato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Macchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Guidolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"De Caro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Porzionato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/s0006-8993(02)04215-4","article-title":"Dopamine inhibits ATP-induced responses in the cat petrosal ganglion in vitro.","volume":"966","author":"Alcayaga","year":"2003","journal-title":"Brain Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/0-387-31311-7_51","article-title":"Carotid body transmitters actions on rabbit petrosal ganglion in vitro.","volume":"580","author":"Alcayaga","year":"2006","journal-title":"Adv. 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