Functional adenosine receptors in human corpora cavernosa

We have demonstrated that adenosine has potent relaxant activity on the rab bit corpus cavernosum, acting through the A(2a) subtype receptor for adenos ine. We now report studies on the identification and functional characteriz ation of adenosine receptors in human penile vessels. To identify A(2) rece ptors in human corpora cavernosa (HCC) we performed binding studies using t he selective radioligand [I-125]PAPA-APEC in membranes from HCC. We found t he presence of a single class of high affinity (K-d= 0.23 +/- 0.06 nM), low capacity (B-max=134 +/- 37 fmoles/mg protein) binding sites. Adenosine and CGS 21680 completely displaced [I-125]PAPA-APEC binding (K-d= 146.7 +/- 64 mu M and 51.52 +/- 27 nM, respectively). Accordingly, in functional studie s adenosine relaxed phenylephrine precontracted HCC with an IC50=2.28 +/- 0 .17 mM. The effect of adenosine was independent from nitric oxide (NO), and was counteracted by the A(2) antagonist CGS 15943. In order to evaluate th e in vivo effect of adenosine, increasing concentrations (6, 60, 600 mu g) of adenosine or prostaglandin E-1 (PGE(1)) (10 mu g) were injected into the corpora cavernosa of four healthy volunteers. Blood flow and erectile resp onse were evaluated at different times by duplex sonography and visual insp ection, respectively. It was found that adenosine increased cavernosal peak blood flow velocity in a time- and dose-dependent manner. The highest conc entrations of injected adenosine elicited a response that was not statistic ally different from that of PGE(1) (10 mu g). However, in contrast to PGE(1 ), a full or partial erection was never obtained. To further investigate th e lack of effect of adenosine on penile tumescence (despite the substantial increase in cavernosal blood flow), in vitro experiments were performed on human deep dorsal penile veins (DDPV) obtained from surgical ligation for impotence. Adenosine did not affect basal tone, but it induced almost compl ete relaxation in noradrenaline-precontracted vein strips with an IC50=1.6 +/- 0.22 mM. Conversely, PGE(1) stimulated a sustained increase in basal to ne. Therefore, the lack of effect of adenosine on penile tumescence could b e due to a simultaneous relaxing activity on penile corpora cavernosa and v eins. In conclusion, our study indicates that adenosine relaxes HCC as well as penile veins without affecting erection, at least at the concentrations we have used. Conversely, PGE(1) relaxes corpora cavernosa as well as aden osine but strongly stimulates vein contraction, allowing penile tumescence.