Inhibitory effects of endomorphin-2 on excitatory synaptic transmission and the neuronal excitability of sacral parasympathetic preganglionic neurons in young rats.
Inhibitory effects of endomorphin-2 on excitatory synaptic transmission and the neuronal excitability of sacral parasympathetic preganglionic neurons in young rats.
复制标题
内啡肽-2对幼龄大鼠兴奋性突触传递和骶副交感神经节前神经元兴奋性的抑制作用
DOI：
10.3389/fncel.2015.00206
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Li YQ
中科院分区：
文献类型：
--
作者：
Chen YB;Huang FS;Fen B;Yin JB;Wang W;Li YQ
膀胱的功能部分由骶副交感神经核（SPN）的副交感节前神经元（PPN）控制。我们最近的工作表明，内吗啡肽-2（EM-2）免疫反应（IR）终末与大鼠SPN中表达μ阿片受体（莫尔）的PPN形成突触。在这里，我们使用全细胞膜片钳方法研究了EM-2对年轻大鼠（24-30日龄）PPN的兴奋性突触传递和神经元兴奋性的影响。通过用荧光示踪剂四甲基罗丹明-葡聚糖（TMR）逆行标记来鉴定PPN。EM-2（3 μM）可显著降低PPN的自发和微小兴奋性突触后电流（sEPSC和mEPSC）的幅度和频率。EM-2在0.282 μM浓度下不仅使61.1%的PPN的静息膜电位（RMPs）降低（半数最大反应），而且使PPN的基电流增加，重复动作电位放电减少。电流-电压关系的分析显示，EM-2诱导的电流在−95 ± 2.5 mV时逆转，并且通过灌注钾通道阻断剂4-氨基吡啶（4-AP）或BaCl 2或向移液器溶液中加入鸟苷5′-[β-硫代]二磷酸三锂盐（GDP-β-S）来抑制，这表明G蛋白偶联内向整流钾（GIRK）通道参与其中。上述EM-2引起的抑制作用可被莫尔选择性拮抗剂D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH 2（CTOP）所消除，表明EM-2对PPN的作用是由莫尔通过突触前和/或突触后机制介导的。EM-2激活突触前和突触后MORs，抑制兴奋性神经递质从突触前末梢的释放和降低PPN的兴奋性，由于其膜电位的超极化，分别。EM-2在脊髓水平对PPN的抑制作用可能解释了吗啡治疗的作用机制和临床上吗啡诱导的膀胱功能障碍。
The function of the urinary bladder is partly controlled by parasympathetic preganglionic neurons (PPNs) of the sacral parasympathetic nucleus (SPN). Our recent work demonstrated that endomorphin-2 (EM-2)-immunoreactive (IR) terminals form synapses with μ-opioid receptor (MOR)-expressing PPNs in the rat SPN. Here, we examined the effects of EM-2 on excitatory synaptic transmission and the neuronal excitability of the PPNs in young rats (24–30 days old) using a whole-cell patch-clamp approach. PPNs were identified by retrograde labeling with the fluorescent tracer tetramethylrhodamine-dextran (TMR). EM-2 (3 μM) markedly decreased both the amplitude and the frequency of the spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) of PPNs. EM-2 not only decreased the resting membrane potentials (RMPs) in 61.1% of the examined PPNs with half-maximal response at the concentration of 0.282 μM, but also increased the rheobase current and reduced the repetitive action potential firing of PPNs. Analysis of the current–voltage relationship revealed that the EM-2-induced current was reversed at −95 ± 2.5 mV and was suppressed by perfusion of the potassium channel blockers 4-aminopyridine (4-AP) or BaCl2 or by the addition of guanosine 5′-[β-thio]diphosphate trilithium salt (GDP-β-S) to the pipette solution, suggesting the involvement of the G-protein-coupled inwardly rectifying potassium (GIRK) channel. The above EM-2-invoked inhibitory effects were abolished by the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), indicating that the effects of EM-2 on PPNs were mediated by MOR via pre- and/or post-synaptic mechanisms. EM-2 activated pre- and post-synaptic MORs, inhibiting excitatory neurotransmitter release from the presynaptic terminals and decreasing the excitability of PPNs due to hyperpolarization of their membrane potentials, respectively. These inhibitory effects of EM-2 on PPNs at the spinal cord level may explain the mechanism of action of morphine treatment and morphine-induced bladder dysfunction in the clinic.
登录
查看更多内容
影响因子：
--
作者：
Blok, BFM
通讯作者：
Blok, BFM
影响因子：
3.3
作者：
GOUARDERES, C;BEAUDET, A;QUIRION, R
通讯作者：
QUIRION, R
影响因子：
2.9
作者：
HISAMITSU, T;DEGROAT, WC
通讯作者：
DEGROAT, WC
DOI：
10.1111/apha.12011
发表时间：
2013-01
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Birder L;Wyndaele JJ
通讯作者：
Wyndaele JJ
影响因子：
2.1
作者：
de Groat, WC
通讯作者：
de Groat, WC