In the present study, we have investigated the possible role of adenos
ine in the hypoxia-mediated increase in adenosine 3',5'-cyclic monopho
sphate (cAMP) in the carotid body. cAMP levels in rabbit carotid bodie
s superfused in vitro for 10 min were increased in the presence of ade
nosine (100 mu M 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 mu M). The specific
A(2)-receptor agonist boxymethyl)phenylethylamino]-5'-N-ethylcarboxami
do adenosine (CGS-21680; 100 nM) also elevated carotid body cAMP level
s, an effect that was blocked by the specific A(2)-antagonist 3,7-dime
thyl-L-propargyl-xanthine (DMPX; 50 mu M). Hypoxia-evoked elevations i
n cAMP were potentiated in the presence of the adenosine-uptake inhibi
tor dipyridamole (100 nM) and blocked by exposure to adenosine-recepto
r antagonists. Our data suggest that the rabbit carotid body contains
specific adenosine receptors (A(2) subtype) that are positively couple
d to adenylate cyclase and that increases in cAMP associated with hypo
xia are mediated by the release of endogenous adenosine.