CAMP Production in Rabbit Carotid Body: Role of Adenosine

In the present study, we have investigated the possible role of adenosine in the hypoxia-mediated increase in adenosine 3',5'-cyclic monophosphate (cAMP) in the carotid body. cAMP levels in rabbit carotid bodies superfused in vitro for 10 min were increased in the presence of adenosine (100 microM and 1.0 mM; maximum increase = 127%, P < 0.01). These effects were reduced by the nonspecific adenosine-receptor antagonist 1,3-dipropyl-8[p-sulfophenyl]xanthine (DPSPX; 10 microM). The specific A2-receptor agonist 2-[4'(2-carboxymethyl)phenylethylamino]-5'-N-ethylcarboxamido adenosine (CGS-21680; 100 nM) also elevated carotid body cAMP levels, an effect that was blocked by the specific A2-antagonist 3,7-dimethyl-L-propargyl-xanthine (DMPX; 50 microM). Hypoxia-evoked elevations in cAMP were potentiated in the presence of the adenosine-uptake inhibitor dipyridamole (100 nM) and blocked by exposure to adenosine-receptor antagonists. Our data suggest that the rabbit carotid body contains specific adenosine receptors (A2 subtype) that are positively coupled to adenylate cyclase and that increases in cAMP associated with hypoxia are mediated by the release of endogenous adenosine.