AUTHOR=Stocco Elena , Emmi Aron , Sfriso Maria Martina , Tushevski Aleksandar , De Caro Raffaele , Macchi Veronica , Porzionato Andrea 

TITLE=Carotid body plastic behavior: evidence for D2–H3 receptor–receptor interactions

JOURNAL=Frontiers in Physiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1422270

DOI=10.3389/fphys.2024.1422270

ISSN=1664-042X

ABSTRACT=<p>Dopamine and histamine receptors D<sub>2</sub>R and H<sub>3</sub>R are G protein-coupled receptors (GPCRs) which can establish physical receptor–receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D<sub>2</sub>R and H<sub>3</sub>R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D<sub>2</sub>R and H<sub>3</sub>R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D<sub>2</sub>R–H<sub>3</sub>R antagonistic functional implications. The CBs of both Sprague–Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D<sub>2</sub>R and H<sub>3</sub>R was performed; thereafter, <italic>in situ</italic> proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D<sub>2</sub>R/H<sub>3</sub>R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D<sub>2</sub>R–H<sub>3</sub>R RRIs. Additionally, D<sub>2</sub>R–H<sub>3</sub>R heterodimers were mainly detected in type I cells (βIII-tubulin-positive cells), but type II cells’ involvement cannot be excluded. RRIs may play a role in functional modulation of CB cells; investigating RRIs in the CB may guide toward the comprehension of its plastic changes and fine regulatory role while also unveiling their possible clinical implications.</p>