Involvement of ATP released from non-neuronal tlssues in presynaptic neuromodulation.

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The results obtained in my research project (04670132) during 1992 to 1993 are summarized as follows.Effects of inhibitors on metabolism by ectonucleotidases of ATP release from non-neuronal tissuesDegradation of exogenously applied ATP in the bathing solution with and without vas deferens and ileal longitudinal muscles of guinea pigs were measured by luciferin-luciferase assay. In medium with a suspended tissue, the amount of ATP in the bathing solution decreased quickly in a time-dependent manner to zero after 15 min. The decay curves of ATP were virtually unaffected by inhibitors of ecto-ATPase such as FSBA and DFDNB and by an ecto-5'-nucleotidase inhibitor, alpha, beta-methylene ADP.In addition, decay curves of ATP released from vas deferens and ileal segment in the presence of noradrenaline and bethanechol, respectively, were unchanged by inhibitors of these ectoenzymes except DFDNB.DFDNB seems to inhibit the release of ATP evoked by the secretagogues from these tissues.Cholinergi … More c neuromodulation evoked by ATP released from a non-neuronal tissueEffects of alpha, beta-methylene ATP (alpha, beta-mATP,a P_<2*>-receptor agonist) on endogenous ACh release evoked by electrical nerve stimulation were evaluated in guinea pig ileal longitudinal muscles. Release of ACh was measured with an HPLC-ECD system. Electrically evoked ACh release was reduced by alpha, beta-mATP at concentrations of 3 ad 30 muM.The reduction by alpha, beta-mATP (30 muM) was not observed in the presence of theophylline (100 muM), a P_1-receptor antagonist. The ATP analog induced the release of ATP in a suramin (P_2-receptor antagonist) -sensitive but Ca^<2+>-and atropine-insensitive manner, suggesting P_2-receptor-mediated release of ATP from the smooth muscle. We conclude from these findings that alpha, beta-mATP dose not reduce ATP release by direct stimulation of presynaptic P_1-receptors, and that endogenous ATP released postjunctionally by the ATP analog is decomposed metabolically to adenosine in the synaose and this adenosine triggers P_1-purinoceptor-sensitive neuromodulation of cholinergic transmission. Less