Carotid body plastic behavior: evidence for D₂-H₃ receptor-receptor interactions

Dopamine and histamine receptors D₂R and H₃R are G protein-coupled receptors (GPCRs) which can establish physical receptor-receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D₂R and H₃R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D₂R and H₃R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D₂R-H₃R antagonistic functional implications. The CBs of both Sprague-Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D₂R and H₃R was performed; thereafter, in situ proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D₂R/H₃R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D₂R-H₃R RRIs. Additionally, D₂R-H₃R 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.