POSTRECEPTOR PATHWAY OF THE ATP-INDUCED RELAXATION IN SMOOTH-MUSCLE OF THE MOUSE VAS-DEFERENS

1 The post-receptor pathway of the ATP relaxant effect in K+-precontra cted vas deferens smooth muscle (VD) was examined. 2 The relaxation to ATP was not antagonized either by 10 muM methylene blue, a cyclic GMP inhibitor, by 10 muM indomethacin, an inhibitor of prostaglandin synt hesis or by 100 muM N(G)-nitro-L-arginine, an inhibitor of NO producti on. 3 The Rp-diastereomer of adenosine 3': 5'-cyclic monophosphorothio ate (Rp-cAMPS) 200 muM, a competitive inhibitor of cyclic AMP signific antly diminished the relaxant response to ATP. 4 Isoprenaline 10 muM, a beta-adrenoceptor agonist, produced a sustained relaxation, inhibite d by Rp-cAMPS, without a significant change in [Ca2+]i, thereby mimick ing the ATP-induced relaxant effect. 5 The level of the phosphorylated myosin light chain in the precontracted VD was significantly lowered by 1000 muM ATP. 6 ATP (1000 muM) and isoprenaline (10 muM) produced t he same increase (+50%) of [cyclic AMP] when applied to a resting VD. 7 The effect of simultaneous increases of [Ca2+]i and of [cyclic AMP] produced by externally applied ATP are discussed. 8 These results sugg est that ATP-induced relaxation in K+-precontracted VD is mediated by the activation of adenylyl cyclase.