Presynaptic localization of the carboxy-terminus epitopes of the μ opioid receptor splice variants MOR-1C and MOR-1D in the superficial laminae of the rat spinal cord

Presynaptic localization of the carboxy-terminus epitopes of the μ opioid receptor splice variants MOR-1C and MOR-1D in the superficial laminae of the rat spinal cord
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DOI:
10.1016/s0306-4522(01)00317-7
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发表时间:
2001-01-01
期刊:
影响因子:
3.3
通讯作者:
Aicher, SA
Aicher, SA
中科院分区:
医学3区
文献类型:
--
作者:
Abbadie, C;Pasternak, GW;Aicher, SA

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阿片样物质在脊髓水平上抑制伤害性传递,可能是通过抑制突触前阿片样物质受体(MORs)的神经递质释放,从而阻止上升通路的激活和疼痛的感知。大多数伤害性初级传入是无髓鞘纤维,其中含有肽,如P物质和/或降钙素基因相关肽。然而,很少有终端同时含有P物质和MOR。最近,我们发现了新的羧基端MOR剪接变体,这些变体位于背角的浅层。我们现在在超微结构水平上报道了这两种MOR-1变异,MOR-1C(外显子7/8/9表位)和MOR-ID(外显子8/9表位)的精确细胞分布。在背角的浅层中,大部分的MOR-1C和MOR-1D标记出现在无髓鞘的轴突。这种分布与MOR-1(外显子4表位)形成对比,后者在树突中同样发现标记。和轴突一样。在许多mor - ic样免疫反应末端存在致密的核心囊泡,这意味着这种剪接变体可能参与突触前抑制从含有肽的传入神经到背角的递质释放。与这一发现一致的是,共聚焦显微镜分析显示,在I-II层中,许多莫尔- ic谱也含有降钙素基因相关肽,而在同一区域,较少的莫尔-1谱含有P物质或降钙素基因相关肽。根据这些发现,我们认为在背角中存在着不同分布的莫尔-1剪接变体以及不同的肽共定位。(c) 2001年。Elsevier Science Ltd.出版。版权所有。
Opioids inhibit nociceptive transmission at the level of the spinal cord, possibly through inhibition of neurotransmitter release by presynaptic mu opioid receptors (MORs) thus preventing the activation of ascending pathways and the perception of pain. Most nociceptive primary afferents are unmyelinated fibers containing peptides such as substance P and/or calcitonin gene-related peptide. However, few terminals contain both substance P and MOR. Recently, we identified new carboxy-terminal MOR splice variants that are localized in the superficial laminae of the dorsal horn. We now report the precise cellular distribution of two of these MOR-1 variants, MOR-1C (exon 7/8/9 epitope) and MOR-ID (exon 8/9 epitope), at the ultrastructural level. In the superficial laminae of the dorsal horn, the majority of the labeling of MOR-1C and MOR-1D was found in unmyelinated axons. This distribution contrasts with that of MOR-1 (exon 4 epitope), in which labeling is equally found in dendrites. and soma, as well as in axons. The presence of dense core vesicles in many of the MOR-IC-like immunoreactive terminals implies that this splice variant might be involved in presynaptic inhibition of transmitter release from peptide-containing afferents to the dorsal horn. Consistent with this finding, confocal microscopy analyses showed that many MOR-IC profiles in laminae I-II also contained calcitonin gene-related peptide, whereas fewer MOR-1 profiles contained either substance P or calcitonin gene-related peptide in this same region.From these findings we suggest that there are differential distributions of MOR-1 splice variants as well as distinct peptide colocalizations in the dorsal horn. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.