Although
adenosine has been implicated in penile erection in human males, the receptor subtype responsible for
adenosine regulation of human corpus cavernosum (HCC) smooth muscle tone is still a matter of debate. Using selective
adenosine agonists and antagonists, we aimed at characterizing the
adenosine receptors mediating relaxation of precontracted (with 1 microM
phenylephrine) HCC strips. HCC specimens were collected from control subjects (organ donors) and from patients with severe vasculogenic
erectile dysfunction (ED). In control subjects,
adenosine and 5'-N-ethyl-carboxamide
adenosine (
NECA) fully relaxed HCC. The selective A(2A) receptor agonist 2-[4-(2-p-carboxy ethyl)phenylamino]-5'-N-ethylcarboxamido
adenosine (CGS21680C) produced only a partial relaxation (30-50%) of HCC, which could be further enhanced by simultaneous application of 100 microM
NECA. The selective A(2B) receptor antagonist N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-il)phenoxy] acetamida (
MRS1706) (10 nM) attenuated
NECA-induced relaxation without affecting CGS21680C action. The A(2A) receptor antagonist 4-{2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl}
phenol (
ZM241385) (50 nM) consistently reduced the actions of both agonists. In contrast to CGS21680C,
NECA-induced relaxation was attenuated when endothelial production of NO and
prostanoids was reduced by 100 microM N(G)-nitro-
l-arginine and 10 microM
indomethacin, respectively. HCC strips from patients with vasculogenic ED were partially resistant to
NECA but kept relaxation to CGS21680C; the remaining effect was sensitive to blockade of A(2A) receptors with 50 nM
ZM241385. Data suggest that
adenosine regulates HCC smooth muscle tone through the activation of two receptor populations, CGS21680C-sensitive (A(2A)) and -insensitive (A(2B)) receptors, located on smooth muscle fibers and on endothelial cells, respectively. Endothelial dysfunction may be correlated with a loss of
adenosine A(2B) receptor activity in penile vessels from men with vasculogenic ED.