Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia.
Neurosci Res. 2011 Nov;71(3):219-25. doi: 10.1016/j.neures.2011.07.1829. Epub 2011 Jul 28.
We established the effect of ATP, which is released together with acetylcholine (ACh), on the non-quantal ACh release (NQR) in rat diaphragm endplates and checked what kind of purine receptors are involved. NQR was estimated by the amplitude of endplate hyperpolarization (the H-effect) following the blockade of postsynaptic nicotinic receptors and cholinesterase. 100 μM ATP reduced the H-effect to 66% of the control. The action of ATP remained unchanged after the inhibition of ionotropic P2X receptors by Evans blue and PPADS, but disappeared after the application of the broad spectrum P2 receptor antagonist suramin, metabotropic P2Y receptor blocker reactive blue 2 and U73122, an inhibitor of phospholipase C. P2Y-mediated regulation is not coupled to presynaptic voltage-dependent Ca(2+) channels. During the simultaneous application of ATP and glutamate (which is another ACh cotransmitter reducing non-quantal release), the additive depressant effect led to a disappearance of the H-effect. This can be explained by the independence of the action of ATP and glutamate. Unlike the effects of purines on the spontaneous quantal secretion of ACh, its non-quantal release is regulated via P2Y receptors coupled to G(q/11) and PLC. ATP thus regulates the neuromuscular synapse by two different pathways.
我们研究了与乙酰胆碱（ACh）一同释放的 ATP 对大鼠膈肌终板非量子型 ACh 释放（NQR）的影响，并检查了涉及的嘌呤受体类型。NQR 通过阻断突触后烟碱型受体和胆碱酯酶后测量终板超极化的幅度（H-效应）来评估。100μM 的 ATP 将 H-效应降低至对照的 66%。埃文斯蓝和 PPADS 抑制离子型 P2X 受体后，ATP 的作用保持不变，但广泛的 P2 受体拮抗剂苏拉明、代谢型 P2Y 受体阻滞剂反应蓝 2 和 PLC 抑制剂 U73122 应用后，ATP 的作用消失。P2Y 介导的调节与突触前电压依赖性 Ca2+通道无关。在同时应用 ATP 和谷氨酸（另一种减少非量子型释放的 ACh 共递质）时，累加的抑制作用导致 H-效应消失。这可以通过 ATP 和谷氨酸作用的独立性来解释。与嘌呤对 ACh 自发量子分泌的作用不同，其非量子型释放通过与 G(q/11)和 PLC 偶联的 P2Y 受体调节。因此，ATP 通过两种不同的途径调节神经肌肉突触。
