Endomorphins: localization, release and action on rat dorsal horn neurons.
Endomorphins: localization, release and action on rat dorsal horn neurons.
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内吗啡肽：对大鼠背角神经元的定位、释放和作用。
DOI：
10.1007/bf02255468
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发表时间：
2000
影响因子：
11
通讯作者：
Kwok,EH
中科院分区：
文献类型：
--
作者：
Dun,NJ;Dun,SL;Wu,SY;Williams,CA;Kwok,EH
内吗啡肽（Endomorphin，Endo）1和2是从牛脑和人脑中分离的两种四肽，被认为是阿片μ受体的内源性配体。本研究采用多学科交叉的研究方法，探讨了Endo在大鼠脊髓背角的定位、释放及其生物学作用。首先，免疫组织化学研究表明，Endo-1-或Endo-2-like免疫反应性（Endo-1-或Endo-2-LI）选择性地表达于占据大鼠背角浅层的纤维样成分中，其也表现出高水平的μ-阿片受体免疫反应性。第二，免疫反应性Endo-2样物质（irEndo）的释放在体外大鼠脊髓电刺激后，背根传入纤维的固定化抗体微探针技术进行了检测。释放的部位对应于板层I和II，其中最高密度的Endo-2-LI纤维被定位。最后，大鼠腰段脊髓切片胶状质（SG）神经元的全细胞膜片钳记录显示，外源性Endo-1和Endo-2有两种不同的作用：（1）抑制由刺激背根进入区引起的兴奋性和/或抑制性突触后电位，（2）SG神经元的超极化。μ阿片受体拮抗剂β-funalcumamine可阻断这两种效应。内吗啡肽阳性纤维在背角浅层的定位和刺激背根传入时irEndo的释放以及Endo通过与μ-阿片受体相互作用抑制SG神经元的活动的观察为Endo作为大鼠背角中μ-阿片受体的内源性配体的作用提供了额外的支持。
Endomorphin (Endo) 1 and 2, two tetrapeptides isolated from the bovine and human brain, have been proposed to be the endogenous ligand for the μ-opiate receptor. A multi-disciplinary study was undertaken to address the issues of localization, release and biological action of Endo with respect to the rat dorsal horn. First, immunohistochemical studies showed that Endo-1- or Endo-2-like immunoreactivity (Endo-1- or Endo-2-LI) is selectively expressed in fiber-like elements occupying the superficial layers of the rat dorsal horn, which also exhibit a high level of μ-opiate receptor immunoreactivity. Second, release of immunoreactive Endo-2-like substances (irEndo) from the in vitro rat spinal cords upon electrical stimulation of dorsal root afferent fibers was detected by the immobilized antibody microprobe technique. The site of release corresponded to laminae I and II where the highest density of Endo-2-LI fibers was localized. Lastly, whole-cell patch clamp recordings from substantia gelatinosa (SG) neurons of rat lumbar spinal cord slices revealed two distinct actions of exogenous Endo-1 and Endo-2: (1) depression of excitatory and/or inhibitory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (2) hyperpolarization of SG neurons. These two effects were prevented by the selective μ-opiate receptor antagonist β-funaltrexamine. The localization of endomorphin-positive fibers in superficial layers of the dorsal horn and the release of irEndo upon stimulation of dorsal root afferents together with the observation that Endo inhibits the activity of SG neurons by interacting with μ-opiate receptors provide additional support of a role of Endo as the endogenous ligand for the μ-opiate receptor in the rat dorsal horn.