THE POTENT RELAXANT EFFECT OF ADENOSINE IN RABBIT CORPORA CAVERNOSA IS NITRIC-OXIDE INDEPENDENT AND MEDIATED BY A(2) RECEPTORS

In the present study the effect of adenosine and adenosine analogues o n rabbit isolated cavernosal smooth muscle has been evaluated in compa rison with the effect of acetylcholine and electrical field stimulatio n. In the presence of guanethidine and indomethacin, acetylcholine and electrical field stimulation relaxed the rabbit corpus cavernosum, wh ich was precontracted with phenylephrine. The nitric oxide synthesis i nhibitor, N-omega-nitro-L-arginine-methylester (L-NAME), greatly reduc ed the relaxation induced by electrical stimulation and completely abo lished the relaxant effect of acetylcholine. A concentration-dependent relaxation of the rabbit corpus cavernosum was produced by adenosine; this effect was not modified by L-NAME, but was reduced by adenosine deaminase. On the other hand, the adenosine-induced relaxation was pot entiated by the inhibitor of adenosine deaminase, erythro-9-(2-hydroxy -3-nonyl)adenine and by the adenosine uptake inhibitor dipyridamole. M oreover, the effect of adenosine was antagonized by the unspecific ade nosine receptor antagonist 8-phenyltheophylline. The receptor subtypes involved in cavernosal relaxation were characterized by using selecti ve receptor antagonists: 1,3-dipropyl-8-cyclopentylxanthine, a blocker of A(1) receptors, did not modify adenosine-induced relaxation. This effect was, however, antagonized by the A(2)-receptor antagonist CGS15 943. A relaxant effect was also obtained with nanomolar concentrations of two synthetic adenosine analogues, the preferential A(2) receptor agonist 5'-N-ethylcarboxamidoadenosine and the A(2a) selective agonist CGS21680. These results demonstrated that adenosine has potent relaxa nt activity on the corpus cavernosum, acting through a mechanism diffe rent from the nitric oxide pathway, and that receptors involved in the effect of adenosine belong to the A(2a) subtype.