Abstract

Effects of stable ATP analogs such as alpha,beta-methylene ATP (alpha,beta-mATP) and beta,gamma-methylene ATP (beta,gamma-mATP) on ATP release and contractile response were evaluated in the vas deferens and ileal longitudinal muscles of guinea pig. In these smooth muscles, administration of alpha,beta-mATP (10, 30 or 100 microM) produced an ATP release accompanied by a transient contraction, but alpha,beta-methylene ADP (30 or 100 microM) or adenosine (30 microM) failed to elicit both the ATP release and the contraction. However, the peak responses of ATP release and contraction to alpha,beta-mATP (100 microM) in the vas deferens appeared around 2 min and 2.62 sec, respectively, after the injection of the drug. Beta,gamma-mATP (10 or 100 microM) caused an ATP release from the vas deferens. The ATP release as well as the contraction evoked by alpha,beta-mATP or beta,gamma-mATP were effectively inhibited by 300 microM suramin, a P2 purinoceptor antagonist. By contrast, ATP release and contractile response to norepinephrine in the vas deferens and those to bethanechol in the ileum were virtually unaffected by this antagonist. Veratridine and ouabain at (30 or 100 microM) caused markedly acetylcholine release from the ileum and norepinephrine release from the vas deferens, respectively. However, alpha,beta-mATP, even in a high concentration of 100 microM, did not elicit any release of acetylcholine or norepinephrine. These findings suggest that alpha,beta-mATP and probably beta,gamma-mATP evoke ATP release from not neuronal but mainly smooth muscular sites by activating suramin-sensitive P2x receptors, implying that "ATP-evoked ATP release system" exists.