Adenosine modulation of neurotransmission in penile erection.

Abstract

1 Adenosine inhibited the noradrenaline-induced contraction of rabbit corpus cavernosum in a dose-dependent manner.

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A2BReceptor Dysfunction

“…Our results showed that, although A 2B receptormediated relaxation can be partially dependent on the production of NO and prostanoids by the endothelium, inhibition of the two pathways with 100 M L-NOARG plus 10 M indomethacin did not further reduce NECA activity, because they might be mutually exclusive. Hemodynamic studies in men showed that penile tumescence due to intracavernosal application of prostaglandin E 1 for treating impotence could be enhanced by adenosine (Chiang et al, 1994), since the nucleoside acts synchronously via smooth muscle fibers and endothelial cells. …”

“…Penile smooth muscle relaxation produced by some endogenous mediators, such as adenosine via A 2B receptors (Chiang et al, 1994), is operated by endothelial NO formation triggered by activation of NO synthase secondary to phosphorylation by protein kinase A or to increases in intracellular Ca 2ϩ . In this context, we investigated whether adenosineinduced relaxation of HCC strips could be mediated by NO production and what would be the receptor subtype involved.…”

“…Adenosine and endothelium-derived NO and prostacyclin are important local mediators of vasodilatation. In several human vascular beds, adenosine A 2 receptors mediate vasodilatation in part through endothelium, possibly by releasing NO (Sobrevia et al, 1997;Li et al, 1998) and prostacyclin (Chiang et al, 1994;Donoso et al, 2005). Other studies, however, failed to demonstrate endothelium-dependent responses in the presence of adenosine (Sabouni et al, 1990;Tsai et al, 1996;Kemp and Cocks, 1999).…”

“…Although the A 2B receptor antagonist MRS1706 (10 nM) antagonized NECA-induced relaxation in HCC strips from control subjects, it was devoid of effect on tissues isolated from patients with vasculogenic ED. Likewise, Chiang et al (1994) showed that adenosine action (probably via A 2B receptors) was greater in intact than in endothelium-denuded rabbit corpora cavernosa, suggesting the involvement of an endotheliumderived relaxing factor. The ability of adenosine analogs to cause relaxation of HCC strips from age-matched patients with nonvasculogenic ED was also evaluated, but their effects were not significantly different from controls.…”

“…Other studies, however, failed to demonstrate endothelium-dependent responses in the presence of adenosine (Sabouni et al, 1990;Tsai et al, 1996;Kemp and Cocks, 1999). Controversy also exists on the receptor subtype (A 2A or A 2B ) predominating on endothelial cells (Chiang et al, 1994;Iwamoto et al, 1994;Sobrevia et al, 1997;Li et al, 1998;Donoso et al, 2005). Since little is known about the adenosine receptor present on endothelial cells of HCC and the impairment of endothelium function may be one of the factors for the attenuation of adenosine receptor-mediated responses, we thought it would be interesting to explore adenosine-induced relaxation of HCC smooth muscle in control subjects after inhibiting endothelial production of NO and prostacyclin compared with patients with vasculogenic impotence exhibiting multiple risk factors for endothelial lesion (e.g., type II diabetes, hypercholesterolemia, hypertension, heavy smoking habits).…”