Bb. Fredholm et al., Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells, BIOCH PHARM, 61(4), 2001, pp. 443-448
The potency of adenosine and inosine as agonists at human adenosine recepto
rs was examined in a functional assay using changes in cyclic AMP (cAMP) fo
rmation in intact Chinese hamster ovary (CHO) cells stably transfected with
the human A(1), A(2A), A(2B), and A(3) receptors. Adenosine increased cAMP
formation in cells expressing the A(2A) (Ec(50): 0.7 muM) and A(2B) (Ec(50
): 24 muM) receptors and inhibited forskolin (0.3-3 muM)-stimulated cAMP fo
rmation in cells expressing the A(1) (Ec(50): 0.7 muM) and A(3) receptors (
Ec(50): 0.29 muM). The potency of adenosine at the A(2A) and A(2B) receptor
s was not altered by the presence of the uptake inhibitor nitrobenzylthioin
osine (NBMPR), whereas it was increased about h-fold by NBMPR at the A(1) a
nd A(3) receptors. In the presence of NBMPR, inosine was a potent agonist (
Ec(50): 7 and 0.08 muM at the A(1) and A(3) receptors, respectively), but w
ith low efficacy especially at the A(3) receptors. No effect of inosine was
seen at the A(2) receptors. Caffeine, theophylline, and paraxanthine shift
ed the dose-response curve for adenosine at the A(1), A(2A), and A(2B) rece
ptors. These results indicate that adenosine is the endogenous agonist at a
ll human adenosine receptors and that physiological levels of this nucleosi
de can activate A(1), A(2A), and A(3) receptors on cells where they are abu
ndantly expressed, whereas pathophysiological conditions are required to st
imulate A(2B) receptors to produce cyclic AMP. (C) 2001 Elsevier Science In
c. All rights reserved.