当前位置: X-MOL 学术Mol. Neurobiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Inhibition of ASIC-Mediated Currents by Activation of Somatostatin 2 Receptors in Rat Dorsal Root Ganglion Neurons
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2021-01-07 , DOI: 10.1007/s12035-020-02257-x
Ting-Ting Liu 1 , Shuang Wei 1, 2 , Ying Jin 1 , Chun-Yu Qiu 1 , Wang-Ping Hu 1
Affiliation  

Somatostatin (SST) and its analogues like octreotide (OCT) have analgesic effect on a variety of pain through peripheral SST receptors (SSTRs). However, the precise molecular mechanisms have not yet been fully elucidated. This research aimed to identify possible antinociceptive mechanisms, showing functional links of the SSTR2 and acid-sensing ion channels (ASICs). Herein, we reported that OCT inhibited the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. OCT concentration-dependently decreased the peak amplitude of acid-evoked inward currents, which were mediated by ASICs. OCT shifted concentration-response curve to protons downwards, with a decrease of 36.53 ± 5.28% in the maximal current response to pH 4.5 in the presence of OCT. OCT inhibited ASIC-mediated currents through SSTR2, since the inhibition was blocked by Cyn 154806, a specific SSTR2 antagonist. The OCT inhibition of ASIC-mediated currents was mimicked by H-89, a membrane-permeable inhibitor of PKA, and reversed by internal treatment of an adenylyl cyclase activator forskolin or 8-Br-cAMP. OCT also decreased the number of action potentials induced by acid stimuli through SSTR2. Finally, peripheral administration of 20 μM OCT, but not 2 μM OCT, significantly relieved nociceptive responses to intraplantar injection of acetic acid in rats. This occurred through local activation of SSTR2 in the injected hindpaw and was reversed following co-application of Cyn 154806. Our results indicate that activation SSTR2 by OCT can inhibit the activity of ASICs via an intracellular cAMP and PKA signaling pathway in rat DRG neurons. These observations demonstrate a cross-talk between ASICs and SSTR2 in peripheral sensory neurons, which was a novel peripheral analgesic mechanism of SST and its analogues.



中文翻译:

通过激活大鼠背根神经节神经元中的生长抑素 2 受体抑制 ASIC 介导的电流

生长抑素 (SST) 及其类似物,如奥曲肽 (OCT),通过外周 SST 受体 (SSTR) 对多种疼痛具有镇痛作用。然而,精确的分子机制尚未完全阐明。这项研究旨在确定可能的镇痛机制,显示 SSTR2 和酸敏感离子通道 (ASIC) 的功能联系。在此,我们报道了 OCT 抑制了大鼠背根神经节 (DRG) 神经元中 ASIC 的电生理活动。OCT 浓度依赖性地降低了由 ASIC 介导的酸诱发的内向电流的峰值幅度。OCT 将浓度-响应曲线向下移动到质子,在 OCT 存在的情况下,对 pH 4.5 的最大电流响应降低了 36.53 ± 5.28%。OCT 通过 SSTR2 抑制 ASIC 介导的电流,由于抑制作用被 Cyn 154806(一种特定的 SSTR2 拮抗剂)阻断。ASIC 介导的电流的 OCT 抑制由 H-89(PKA 的膜渗透抑制剂)模拟,并通过腺苷酸环化酶激活剂毛喉素或 8-Br-cAMP 的内部处理逆转。OCT 还通过 SSTR2 减少了由酸刺激诱导的动作电位的数量。最后,外周给药 20 μM OCT,而不是 2 μM OCT,可显着减轻大鼠足底注射醋酸的伤害性反应。这通过注射后爪中 SSTR2 的局部激活发生,并在共同应用 Cyn 154806 后逆转。我们的结果表明,OCT 激活 SSTR2 可以通过大鼠 DRG 神经元中的细胞内 cAMP 和 PKA 信号通路抑制 ASIC 的活性。

更新日期:2021-01-07
down
wechat
bug