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

## TL;DR

This study shows that dopamine and histamine receptors in the carotid body can form complexes, suggesting a new way these receptors interact to regulate body functions.

## Contribution

The study provides first evidence of D2R–H3R receptor–receptor interactions in the carotid body.

## Key findings

- D2R and H3R receptors colocalize in the carotid body of rats and humans.
- D2R–H3R heterodimers are primarily found in type I cells of the carotid body.
- Receptor–receptor interactions may modulate carotid body function and plasticity.

## Abstract

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.