We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A(2B) receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A(2B) and dopamine D(2) receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats. The effect of A2B adenosine and D(2) dopamine agonists and antagonists applied alone or in combination were studied on basal (20% O(2)) and hypoxia (10% O(2))-evoked release of CA and cAMP content of CB. We have found that adenosine A(2) agonists and D(2) antagonists dose-dependently increased basal and evoked release CA from the CB while A(2) antagonists and D(2) agonists had an inhibitory action. The existence of A(2B)-D(2) receptor interaction was established because the inhibitory action of A(2) antagonists was abolished by D(2) antagonists, and the stimulatory action of A(2) agonists was abolished by D(2) agonists. Further, A(2) agonists increased and D(2) 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(2B) adenosine and D(2) dopamine receptors exist in rat CB and would explain the dopamine-adenosine interactions on ventilation previously observed.