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

非神经元组织释放的 ATP 参与突触前神经调节。

基本信息

批准号：
04670132
负责人：
KATSURAGI Takeshi
金额：
$ 1.15万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

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

我在1992 - 1993年的研究项目（04670132）中获得的结果总结如下：用荧光素-荧光素酶法测定外源性ATP在有输精管和不含回肠纵向肌的豚鼠沐浴液中的降解情况。在有悬浮组织的培养基中，洗浴液中ATP的量在15分钟后以时间依赖性的方式迅速下降到零。ATP的衰减曲线几乎不受外链ATP酶抑制剂如FSBA和DFDNB以及外链5'-核苷酸酶抑制剂α， β -亚甲基ADP的影响。此外，除DFDNB外，输精管和回肠段在去甲肾上腺素和乙二酚存在下释放的ATP的衰减曲线不受这些外酶抑制剂的影响。DFDNB似乎可以抑制这些组织中分泌物引起的ATP的释放。研究了α、β -亚甲基ATP （α、β - matp，一种P_<2*>受体激动剂）对电刺激豚鼠回肠纵肌内源性乙酰胆碱能释放的影响。HPLC-ECD法测定乙酰胆碱释放量。在浓度为3和30 muM时，α、β - mapp可减少电诱发的乙酰胆碱释放。在p_1受体拮抗剂茶碱（100 muM）存在时，未观察到α， β - matp （30 muM）的减少。ATP类似物诱导ATP以素胺（p_2受体拮抗剂）敏感但Ca^<2+>和阿托品不敏感的方式释放，提示p_2受体介导的ATP从平滑肌释放。我们从这些发现中得出结论，α、β - matp不会通过直接刺激突触前p_1受体来减少ATP的释放，并且ATP类似物在突触后释放的内源性ATP在突触内代谢分解为腺苷，腺苷触发p_1 -嘌呤受体敏感的胆碱能传递神经调节。少