Name: | Description: | Size: | Format: | |
---|---|---|---|---|
517.31 KB | Adobe PDF |
Advisor(s)
Abstract(s)
ABSTRACT
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
M 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 A2A 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 M NECA. The selective A2B 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 A2A 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, NECAinduced
relaxation was attenuated when endothelial production
of NO and prostanoids was reduced by 100 M NG-nitro-Larginine
and 10 M 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 A2A receptors with 50 nM
ZM241385. Data suggest that adenosine regulates HCC
smooth muscle tone through the activation of two receptor
populations, CGS21680C-sensitive (A2A) and -insensitive (A2B)
receptors, located on smooth muscle fibers and on endothelial
cells, respectively. Endothelial dysfunction may be correlated
with a loss of adenosine A2B receptor activity in penile vessels
from men with vasculogenic ED.
Description
Keywords
Citation
J Pharmacol Exp Ther. 2006;319(1):405-13
Publisher
Williams & Wilkins