• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels.
【24h】

Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels.

机译：通过P2Y受体介导的电压门控Ca2 +通道的抑制，自动抑制PC12细胞和交感神经元释放递质。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Although feedback inhibition of noradrenaline release by coreleased nucleotides is a well known phenomenon, it remained unclear which P2 receptor subtypes and associated signalling cascades may be involved. In the rat pheochromocytoma cell line PC12, 2-methylthio-ADP reduced noradrenaline release triggered by K+ depolarization more potently than ADP and ATP, whereas UDP or UTP failed to do so. The inhibition by ADP was abolished by pertussis toxin and antagonized by reactive blue 2, 2-methylthio-AMP, and AR-C69931MX, but not by suramin. AR-C69931MX acted as a competitive antagonist with an apparent affinity of 2 nm, but did not alter noradrenaline release, when PC12 cells were continuously superfused. However, when the superfusion was halted during K+ depolarization, release was significantly reduced and this inhibition was attenuated by AR-C69931MX, thus revealing ongoing autoinhibition. Rises in cellular cyclic AMP did not alter depolarization-evoked release nor its reduction by ADP, even though the nucleotide did inhibit cyclic AMP accumulation. ADP and the direct Ca2+ channel blocker Cd2+ inhibited voltage-activated Ca2+ currents, but not ATP-induced currents, and both agents reduced K+-evoked, but not ATP-evoked, release. Hence, if voltage-gated Ca2+ channels do not contribute to stimulation-evoked release, ADP fails to exert its inhibitory action. In primary cultures of rat sympathetic neurons, ADP also reduced Ca2+ currents and K+-evoked noradrenaline release, and AR-C69931MX acted again as competitive antagonist with an apparent affinity of 3 nm. These results show that P2Y12 receptors mediate an autoinhibition of transmitter release from PC12 cells and sympathetic neurons through an inhibition of voltage-gated Ca2+ channels.
机译：尽管共释放的核苷酸对去甲肾上腺素释放的反馈抑制是众所周知的现象，但仍不清楚可能涉及哪些P2受体亚型和相关的信号级联。在大鼠嗜铬细胞瘤细胞系PC12中，2-甲硫基-ADP比ADP和ATP更有效地减少了K +去极化触发的去甲肾上腺素释放，而UDP或UTP则没有。百日咳毒素消除了ADP的抑制作用，活性蓝2、2-甲硫基AMP和AR-C69931MX则拮抗了ADP的抑制作用，但苏拉明却没有。当PC12细胞持续融合时，AR-C69931MX充当竞争性拮抗剂，表观亲和力为2 nm，但没有改变去甲肾上腺素的释放。但是，当在K +去极化过程中中止灌注时，释放显着减少，并且这种抑制作用会被AR-C69931MX减弱，从而显示出正在进行的自动抑制作用。即使细胞中的核苷酸确实抑制了环状AMP的积累，其在细胞环状AMP中的升高也不会改变去极化引起的释放或ADP的释放。 ADP和直接的Ca2 +通道阻滞剂Cd2 +抑制了电压激活的Ca2 +电流，但抑制了ATP诱导的电流，两种药物均降低了K +诱发的释放，但不引起ATP诱发的释放。因此，如果电压门控的Ca2 +通道对刺激诱发的释放没有贡献，则ADP无法发挥其抑制作用。在大鼠交感神经元的原代培养中，ADP还降低了Ca2 +电流和K +诱发的去甲肾上腺素的释放，AR-C69931MX再次充当竞争性拮抗剂，表观亲和力为3 nm。这些结果表明，P2Y12受体通过抑制电压门控的Ca2 +通道来介导PC12细胞和交感神经元递质释放的自动抑制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号