Carotid body plastic behavior: evidence for D-H receptor-receptor interactions.

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