Presynaptic NK1 Receptor Activation by Substance P Suppresses EPSCs via Nitric Oxide Synthesis in the Rat Insular Cortex
Presynaptic NK1 Receptor Activation by Substance P Suppresses EPSCs via Nitric Oxide Synthesis in the Rat Insular Cortex
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DOI：
10.1016/j.neuroscience.2020.12.012
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发表时间：
2020-12
期刊：
影响因子：
3.3
通讯作者：
Sachie Matsumura;Kiyofumi Yamamoto;Y. Nakaya;Kazunori O’Hashi;K. Kaneko;H. Takei;Hiromasa Tsuda;T. Shirakawa;Masayuki Kobayashi
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文献类型：
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作者：
Sachie Matsumura;Kiyofumi Yamamoto;Y. Nakaya;Kazunori O’Hashi;K. Kaneko;H. Takei;Hiromasa Tsuda;T. Shirakawa;Masayuki Kobayashi
P 物质 (SP) 调节大脑皮层 GABAA 受体介导的抑制性突触传递；然而，SP 介导的兴奋性突触传递调节仍然知之甚少。我们对锥体神经元进行了全细胞膜片钳记录，以检查 SP 对岛皮层 (IC) 中 AMPA 受体介导的兴奋性突触后电流 (EPSC) 的影响，岛皮层 (IC) 参与伤害性信息处理。首先，检查了由最小电刺激 (eEPSC) 诱发的 EPSC，包括逐步 EPSC 和故障事件。 SP 剂量依赖性抑制平均 eEPSC 振幅，部分原因是 eEPSC 失败率增加。 SP 诱导的 eEPSC 抑制伴随着配对脉冲比的增加，并可通过预先施用 NK1 受体拮抗剂 SR140333 来抑制。 [Sar9,Met(O2)11]-物质 P 是一种 NK1 受体选择性激动剂，模拟 SP 对 eEPSC 的作用，并降低微型 EPSC (mEPSC) 的频率，而不改变平均 mEPSC 振幅。考虑到大脑皮层中的大多数 NK1 受体在一氧化氮合酶 (NOS) 阳性 GABA 能神经元中表达，SP 诱导的对 EPSC 的抑制作用可能是由这种 GABA 能神经元亚型中的一氧化氮 (NO) 介导的。使用荧光探针 DAX-J2 Red 的 NO 成像支持了这一假设：SP 增加了一些 GABA 能神经元中 DAX-J2 Red 的荧光强度。此外，L-NAME（一种 NOS 抑制剂）和 PTIO（一种 NO 清除剂）都能减轻 SP 诱导的 eEPSC 抑制。这些结果表明，突触前 NK1 受体的激活通过激活 GABA 能神经元中的 NO 合成途径，有助于 SP 诱导的 eEPSC 抑制。 （246字）
Substance P (SP) regulates inhibitory synaptic transmission mediated by GABAAreceptors in the cerebral cortex; however, SP-mediated regulation of excitatory synaptic transmission remains poorly understood. We performed whole-cell patch-clamp recordings from pyramidal neurons to examine the effects of SP on excitatory postsynaptic currents (EPSCs) mediated via AMPA receptors in the insular cortex (IC), which is involved in nociceptive information processing. First, EPSCs evoked by minimal electrical stimulation (eEPSCs) including stepwise EPSCs and failure events, were examined. SP dose-dependently suppressed mean eEPSC amplitude, partially due to an increase in the failure rate of eEPSCs. The SP-induced suppression of eEPSCs was accompanied by an increase in the paired-pulse ratio and was inhibited by the preapplication of SR140333, an NK1 receptor antagonist. [Sar9,Met(O2)11]-substance P, an NK1 receptor-selective agonist, mimicked the effects of SP on eEPSCs and decreased the frequency of miniature EPSCs (mEPSCs) without changing the average mEPSC amplitude. Considering that most NK1 receptors in the cerebral cortex are expressed in nitric oxide synthase (NOS)-positive GABAergic neurons, the SP-induced suppressive effect on EPSCs may be mediated by nitric oxide (NO) in this subtype of GABAergic neurons. NO imaging using the fluorescent probe DAX-J2 Red supports this hypothesis: SP increased the fluorescence intensity of DAX-J2 Red in some GABAergic neurons. Furthermore, both L-NAME, an NOS inhibitor, and PTIO, an NO scavenger, diminished the SP-induced suppression of eEPSCs. These results suggest that the activation of presynaptic NK1 receptors contributes to SP-induced eEPSC suppression by activating the NO synthesis pathway in GABAergic neurons. (246 words)