Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice.
Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice.
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DOI：
10.1016/j.jphs.2019.06.010
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发表时间：
2019-06
影响因子：
3.5
通讯作者：
K. Migita;A. Nishimura;Fumihiro Eto;K. Koga;Taichi Matsumoto;K. Terada;Shuji Hara;K. Honda
中科院分区：
文献类型：
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作者：
K. Migita;A. Nishimura;Fumihiro Eto;K. Koga;Taichi Matsumoto;K. Terada;Shuji Hara;K. Honda
胆碱能神经元在大脑的高级功能中起着重要的作用，如记忆、认知和伤害感觉。然而，刺激全脑所有毒蕈碱m1受体导致减轻部分坐骨神经结扎（PSNL）引起的机械超敏反应的确切机制尚未得到研究。因此，我们研究了哪一种GABA受体亚型参与减轻psnl诱导的机械超敏反应，这种超敏反应是由脑室内给药毒蕈碱m1受体激动剂McN-A-343引起的。给予gaba受体拮抗剂双管碱对mcn - a -343诱导的PSNL小鼠的抗超敏反应没有改变，而gaba受体拮抗剂CGP35348则剂量依赖性地抑制了抗超敏反应。此外，CGP35348增加naïve小鼠的机械超敏反应，超敏反应被NMDA受体拮抗剂MK-801和D-AP5阻断。此外，毒蕈碱m1受体与gabab1受体和NMDA受体亚基GluN2A在大脑的大片区域共定位。因此，这些结果表明，整个大脑中毒蕈碱m1受体的激活通过gabab受体减少神经损伤诱导的机械超敏反应，gabab受体的激活通过NMDA受体调节谷氨酸能的传递。
Cholinergic neurons play an important role in the higher functions of the brain, such as the memory, cognition, and nociception. However, the exact mechanism behind how the stimulation of all the muscarinic M1receptors in the entire brain results in the alleviation of partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity has not been investigated. Thus, we examined which subtype of GABA receptor was involved in the alleviation of PSNL-induce mechanical hypersensitivity produced by an intracerebroventricular administration of a muscarinic M1receptor agonist, McN-A-343. Administering a GABAAreceptor antagonist, bicuculline, resulted in no changes to the McN-A-343-induced anti-hypersensitivity in PSNL mice whereas a GABABreceptor antagonist, CGP35348, dose-dependently inhibited the anti-hypersensitivity. Furthermore, CGP35348 increased mechanical hypersensitivity in naïve mice, and the hypersensitivity was blocked by NMDA receptor antagonists, MK-801 and D-AP5. Additionally, muscarinic M1receptors colocalized with GABAB1receptors and an NMDA receptor subunit, GluN2A, in a large region of the brain. Consequently, these results suggest that the activation of muscarinic M1receptors in the entire brain reduces nerve injury-induced mechanical hypersensitivity via the GABABreceptors, and the activation of the GABABreceptors regulates glutamatergic transmission via NMDA receptors.