Endomorphin-2 axon terminals contact mu-opioid receptor-containing dendrites in trigeminal dorsal horn

Endomorphin-2 axon terminals contact mu-opioid receptor-containing dendrites in trigeminal dorsal horn
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DOI:
10.1016/s0006-8993(03)02678-7
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发表时间:
2003-07-11
期刊:
影响因子:
2.9
通讯作者:
Zadina, JE
Zadina, JE
中科院分区:
医学3区
文献类型:
--
作者:
Aicher, SA;Mitchell, JL;Zadina, JE

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内吗啡代表了一组新的内源性阿片肽,它们与Mu-阿片受体(MOR1)具有高亲和力。内吗啡肽-2高密度表达于脊髓和三叉神经背角,定位于初级传入神经。如果内吗啡素-2是MOR1的内源性配体,我们有望在细胞内找到与多肽密切相关的受体。我们使用双标记免疫细胞化学方法结合电子显微镜来确定内吗啡-2和MOR1之间是否存在功能相互作用的细胞底物。我们证实了内吗啡肽-2在三叉神经背角的无髓轴突和轴突终末的定位。这些内吗啡-2轴突中有一小部分含有MOR1,但许多内吗啡-2终末的树突靶点含有MOR1。与以前的研究一致,内吗啡-2主要存在于致密的核心小泡中,而MOR1主要位于非突触部位。这些形态特征与多肽在突触外释放,其受体可能位于突触连接的远端的假说相一致。这些解剖学数据支持内吗啡-2是三叉神经背角MORS的配体的假说,特别是在突触后部位。(C)2003 Elsevier Science B.V.保留所有权利。
The endomorphins represent a novel group of endogenous opioid peptides that have high affinity for the mu-opioid receptor (MOR1). Endomorphin-2 is present in high density in the spinal and trigeminal dorsal horns and is localized to primary afferents. If endomorphin-2 were an endogenous ligand for the MOR1, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemical methods combined with electron microscopy to determine if a cellular substrate exists for functional interactions between endomorphin-2 and MOR1. We confirmed the localization of endomorphin-2 to unmyelinated axons and axon terminals in the trigeminal dorsal horn. A small proportion of these endomorphin-2 axons contained MOR1, but many of the dendritic targets of endomorphin-2 terminals contained MOR1. Consistent with previous studies, endomorphin-2 was contained primarily in dense core vesicles and MOR1 was located primarily at non-synaptic sites. These morphological characteristics are consistent with the hypothesis that peptides are released extra-synaptically and their receptors may be located at sites distal to the synaptic junction. These anatomical data support the hypothesis that endomorphin-2 is a ligand for MORs in the trigeminal dorsal horn, particularly at postsynaptic sites. (C) 2003 Elsevier Science B.V. All rights reserved.