Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT2A and 5-HT3 receptors
Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT2A and 5-HT3 receptors
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DOI：
10.1016/j.ejphar.2013.01.058
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发表时间：
2013-02-28
影响因子：
5
通讯作者：
Ito, Shigeo
中科院分区：
文献类型：
--
作者：
Iwasaki, Takeyuki;Otsuguro, Ken-ichi;Ito, Shigeo
5-羟色胺（5-HT）是脊髓下行神经纤维释放的重要物质，在脊髓运动和伤害感受等功能中起重要作用。5-HT 2A和5-HT 3受体被认为有助于脊髓抗伤害感受，尽管它们的激活也有助于神经元兴奋。在新生脊髓中，5-HT受体激动剂DL-对氯苯丙胺（pCA）可抑制A纤维诱发的单突触反射电位（MSR）和C纤维诱发的慢腹根电位（sVRP）。pCA介导的抑制作用可被酮色林（5-HT_2A受体拮抗剂）和托烷司琼（5-HT_3受体拮抗剂）逆转。在这种情况下，5-HT的作用被酮色林拮抗，而不是托烷司琼。GABA（A）受体拮抗剂荷包牡丹碱（bicuculline）和甘氨酸受体拮抗剂士的宁（strychnine）可减弱pCA对sVRP的抑制作用。此外，酮色林抑制pCA诱发的γ-氨基丁酸（GABA）和甘氨酸的释放，而托烷司琼抑制pCA诱发的5-HT的释放。这些结果表明，由pCA释放的5-HT激活5-HT 2A受体，这反过来又刺激GABA/甘氨酸的释放，从而阻断脊髓伤害性通路。5-HT 3受体可能通过正反馈过程参与促进5-HT释放。(C)2013爱思唯尔有限公司版权所有。
Serotonin (5-HT) released from descending fibers plays important roles in spinal functions such as locomotion and nociception. 5-HT2A and 5-HT3 receptors are suggested to contribute to spinal antinociception, although their activation also contributes to neuronal excitation. In the neonatal spinal cord, DL-p-chloroamphetamine (pCA), a 5-HT releaser, inhibited both A fiber-evoked monosynaptic reflex potential (MSR) and C fiber-evoked slow ventral root potential (sVRP). The pCA-mediated inhibition was reversed by ketanserin (a 5-HT2A receptor antagonist) and tropisetron (a 5-HT3 receptor antagonist). Bath-applied 5-HT also inhibited MSR and sVRP; in this case, the actions of 5-HT were antagonized by ketanserin, but not by tropisetron. The pCA-evoked inhibition of sVRP was reduced by bicuculline (a GABA(A) receptor antagonist) and strychnine (a glycine receptor antagonist). Furthermore, ketanserin inhibited the pCA-evoked release of gamma-aminobutyric acid (GABA) and glycine, while tropisetron inhibited the pCA-evoked release of 5-HT. These results suggest that 5-HT released by pCA activates 5-HT2A receptors, which in turn stimulates the release of GABA/glycine and thereby blocks the spinal nociceptive pathway. 5-HT3 receptors may be involved in the facilitation of 5-HT release via a positive feedback process. (C) 2013 Elsevier B.V. All rights reserved.