Opioid peptides inhibit excitatory but not inhibitory synaptic transmission in the rat dorsal motor nucleus of the vagus
Opioid peptides inhibit excitatory but not inhibitory synaptic transmission in the rat dorsal motor nucleus of the vagus
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DOI：
10.1523/jneurosci.22-08-02998.2002
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发表时间：
2002-04-15
影响因子：
5.3
通讯作者：
Travagli, RA
中科院分区：
文献类型：
--
作者：
Browning, KN;Kalyuzhny, AE;Travagli, RA
当阿片肽应用于脑干时，产生胃肠道抑制和增加摄食。本研究旨在确定阿片肽在迷走神经背运动核（DMV）突触传递中的作用以及多阿片受体的定位。在大鼠的薄脑干切片中，对胃肠道突出的DMV神经元进行全细胞记录。电刺激孤束核诱发EPSCs和IPSCs。在所有神经元中，蛋氨酸（Met）脑啡肽（0.003- 30 muM）抑制EPSCs的峰值振幅。纳洛酮（1毫微克）和纳洛嗪（0.2毫微克）均可阻止这种作用。引起的成对脉冲的比例增加表明抑制是由于突触前受体的作用。这种突触前抑制作用可被[D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-脑啡肽（0.1 muM）和镇痛二肽kyotorphin （10 muM）模拟，但不能被环[D-Pen(2), D-Pen(5)]-脑啡肽（1 muM）和反式3,4-二氯- n -甲基- n -[2-（1-吡啶基）-环己基]苯乙酰胺甲磺酸（1 muM）模拟。相比之下，诱导的IPSCs的振幅没有被Met-enkephalin或任何阿片受体选择性激动剂改变。免疫组织化学研究表明，DMV神经元的神经末梢对谷氨酸共定位的mu-阿片受体具有免疫反应性，但对谷氨酸脱羧酶没有免疫反应性。这些结果表明，在DMV内，mu-阿片受体存在于兴奋性神经末梢，而不存在于GI运动神经元的抑制性输入。这种特异性可能意味着阿片肽对胃肠道功能的中枢抑制作用是针对特定途径的。
Opioid peptides produce gastrointestinal inhibition and increase feeding when applied to the brainstem. The present studies were designed to determine the actions of opioid peptides on synaptic transmission within the dorsal motor nucleus of the vagus (DMV) and the localization of mu-opioid receptors. Whole-cell recordings were made from identified gastrointestinal-projecting DMV neurons in thin brainstem slices of the rat. Electrical stimulation of the nucleus of the tractus solitarius evoked EPSCs and IPSCs. In all neurons tested, methionine (Met) enkephalin (0.003- 30 muM) inhibited the peak amplitude of the EPSCs. The effect was prevented by naloxone (1 muM) as well as by naloxonazine (0.2 muM). An increase in the ratio of the evoked paired pulses indicated that the inhibition was attributable to actions at presynaptic receptors. This presynaptic inhibitory action was mimicked by [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (0.1 muM) and the analgesic dipeptide kyotorphin (10 muM) but not by cyclic[D-Pen(2), D-Pen(5)]-enkephalin (1 muM) and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate (1 muM). In contrast, the amplitude of evoked IPSCs was not altered either by Met-enkephalin or by any of the opioid receptor-selective agonists. Immunohistochemical studies revealed that nerve terminals apposing DMV neurons showed immunoreactivity to mu-opioid receptors colocalized with glutamate immunoreactivity but not glutamic acid decarboxylase immunoreactivity. These results suggest that within the DMV, mu-opioid receptors are present on the nerve terminals of excitatory but not inhibitory inputs to GI motoneurons. Such specificity may imply that the central inhibitory action of opioid peptides on gastrointestinal function targets selected pathways.