An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

<jats:title>Abstract</jats:title><jats:p>We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A<jats:sub>2B</jats:sub> receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A<jats:sub>2B</jats:sub> and dopamine D<jats:sub>2</jats:sub> receptors present in chemoreceptor cells. Experiments were performed <jats:italic>in vitro</jats:italic> in CB from 3 months rats. The effect of A<jats:sub>2B</jats:sub> adenosine and D<jats:sub>2</jats:sub> dopamine agonists and antagonists applied alone or in combination were studied on basal (20%O<jats:sub>2</jats:sub>) and hypoxia (10%O<jats:sub>2</jats:sub>)‐evoked release of CA and cAMP content of CB. We have found that adenosine A<jats:sub>2</jats:sub> agonists and D<jats:sub>2</jats:sub> antagonists dose‐dependently increased basal and evoked release CA from the CB while A<jats:sub>2</jats:sub> antagonists and D<jats:sub>2</jats:sub> agonists had an inhibitory action. The existence of A<jats:sub>2B</jats:sub>‐D<jats:sub>2</jats:sub> receptor interaction was established because the inhibitory action of A<jats:sub>2</jats:sub> antagonists was abolished by D<jats:sub>2</jats:sub> antagonists, and the stimulatory action of A<jats:sub>2</jats:sub> agonists was abolished by D<jats:sub>2</jats:sub> agonists. Further, A<jats:sub>2</jats:sub> agonists increased and D<jats:sub>2</jats:sub> agonist decreased cAMP content in the CB; their co‐application eliminated the response. The present results provide direct pharmacological evidence that an antagonistic interaction between A<jats:sub>2B</jats:sub> adenosine and D<jats:sub>2</jats:sub> dopamine receptors exist in rat CB and would explain the dopamine‐adenosine interactions on ventilation previously observed.</jats:p>