The A_2B-D₂ Receptor Interaction that Controls Carotid Body Catecholamines Release Locates Between the Last Two Steps of Hypoxic Transduction Cascade

Abstract

We have recently demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A_2B receptors. Here, we have investigated the hypothesis that this control is exerted via an interaction between adenosine A_2B and dopamine D₂ receptors present in chemoreceptor cells and if it is, the location of this interaction on the CB hypoxic transduction cascade. Experiments were performed in vitro in CB from 3 months rats. The effect of adenosine A_2B and dopamine D₂ receptor agonists applied alone or conjunctly, was studied on the basal and evoked release (10% O₂ and ionomycin) of CA from CB. We have observed that the inhibitory action of propylnorapomorphine, a D₂ selective agonist, on the normoxic and 10%O₂-evoked release of CA was abolished by NECA, an A₂ agonist, meaning that an interaction between the D₂ and A_2B receptors controls the release of CA from CB. Further, propylnorapomorphine inhibits the release of CA evoked by ionomycin, being this effect totally reversed by NECA. The present results provide direct pharmacological evidence that A_2B and D₂ receptors interact to modulate the release of CA from rat CB between the steps of Ca²⁺ entry and increase in intracellular free Ca²⁺, and the activation of exocytosis and neurotransmitter release, of the stimulus-secretion coupling process.