STUDIES ON THE MECHANISMS INVOLVED IN THE ATP-INDUCED RELAXATION IN HUMAN AND RABBIT CORPUS CAVERNOSUM

Abstract

The effect of ATP in human and rabbit corpus cavernosum (CC) smooth muscle was investigated. Strips of human CC were vertically mounted in an organ bath and the tonic tension was recorded. ATP (0.1-3 mM) induced a concentration-dependent relaxant effect, with a pD 2 value of 3.01 +/− 0.3. The purine-induced relaxation was not affected by L-NAME (100 micro M). In rabbit CC, ATP also induced a concentration-dependent relaxation, which was not influenced by L-NAME or by indomethacin (3 micro M), with a pD 2 value of 3.1 +/− 0.4. The ATP-induced relaxant effect in rabbit CC was increased by both the inhibitor of adenosine reuptake, dipyridamole (3 micro M) and by the inhibitor of adenosine deaminase, EHNA (0.3 micro M). Moreover CGS 15943 (3 micro M), an A 2a adenosine antagonist, reduced the ATP-induced relaxation. UTP was not able to produce relaxation. The two ATP analogues 2-methylthioATP and alpha, beta-methylene ATP were able to induce relaxation in rabbit CC, with the following order of potency: 2-methylthioATP > ATP > alpha, beta-methylene ATP thus suggesting a role for P 2y receptors. However, reactive blue (500 micro M), an unspecific P 2y antagonist, did not modify the ATP relaxant response. The inhibition of phospholipase C by U73122 (3 micro M) and of the endoplasmic reticulum Ca 2+ ATPase by thapsigargin (1 micro M) did not modify the ATP-induced relaxation. The P 2x specific antagonist PPADS (30 micro M) and suramine (500 micro M) were not able to modify the ATP relaxation either in the absence or presence of CGS 15943 (3 micro M). These results confirm that ATP acts as a potent and NO-independent relaxant agent of human and rabbit CC. Our findings also show that the ATP effect is partially attributable to the metabolic breakdown of ATP to adenosine, which acts through A 2a receptor stimulation, but is also due to a direct stimulation of P 2 receptors that are different from the classical P 2y and P 2x receptor subtypes for ATP.