Adenosine Mediates Hypercapnic Response in the Rat Carotid Body via A_2A and A_2B Receptors

Adenosine is one of the key neurotransmitters involved in hypoxic signaling in the carotid body (CB), and it was recently found to have a modulatory role in mediating hypercapnic sensitivity in the CB. Herein we have investigated the contribution of adenosine to the hypercapnic response in the rat CB and studied the adenosine receptors responsible for this effect. Experiments were performed in Wistar rats. Adenosine release in normoxia (21% O₂) and in response to hypercapnia (10% CO₂) was quantified by HPLC. Carotid sinus nerve (CSN) chemosensory activity was evaluated in response to hypercapnia in the absence and presence of ZM241385 (300 nM), an A₂ antagonist, and SCH58261 (20 nM), a selective A_2A antagonist. Hypercapnia increased the extracellular concentrations of adenosine by 50.01%. Both, ZM241385 and SCH58261, did not modify significantly the basal frequency of discharges of the CSN. Also, ZM241385 and SCH58261 did not modify the latency time and the time to peak in CSN chemosensory activity. CSN activity evoked by hypercapnia decreased by 58.82 and 33.59% in response to ZM241385 and to SCH58261, respectively. In conclusion, the effect of adenosine in mediating the hypercapnic response in the rat CB involves an effect on A_2A and A_2B adenosine receptors.