Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand
Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand
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DOI：
10.1016/j.neures.2009.04.014
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发表时间：
2009-08-01
影响因子：
2.9
通讯作者：
Misawa, Hidemi
中科院分区：
文献类型：
--
作者：
Moriwaki, Yasuhiro;Watanabe, Yosuke;Misawa, Hidemi
分泌型哺乳动物Ly6/尿激酶纤溶酶原激活物受体相关蛋白-1 （SLURP-1）是最近发现的烟碱乙酰胆碱受体α 7亚基的内源性配体。SLURP-1也是常染色体隐性掌足底角化病malde Meleda的致病基因。虽然SLURP-1在角化细胞发育和分化中的功能已被广泛研究，但其在神经系统中的作用知之甚少。在本研究中，我们分析了SLURP-1在大鼠脊髓中的表达，因为许多研究表明脊髓烟碱乙酰胆碱受体是疼痛传递的重要调节剂。我们在脊髓背角检测到强烈的SLURP-1免疫反应性，特别是在I层和II层外。在背根神经节中，在中小神经元中检测到SLURP-1的免疫反应性，原位杂交也发现了SLURP-1 mRNA的存在。在脊髓背角和无毛皮肤中，SLURP-1的荧光标记部分与降钙素基因相关肽（CGRP）或P物质（SP）重叠，电镜分析显示SLURP-1与SP或CGRP共定位在脊髓浅层终末的大突触囊泡中。最后，坐骨神经轴切术降低了SLURP-1的免疫反应性水平，与SP和CGRP在同侧浅背角的水平平行。这些发现表明SLURP-1在初级肽能感觉神经元的一个亚群中表达。(C) 2009爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is a recently identified, endogenous ligand of the alpha 7 subunit of nicotinic acetylcholine receptors. SLURP-1 is also the causative gene for an autosomal recessive palmoplantar keratoderma, Mal de Meleda. Although the function of SLURP-1 in keratinocyte development and differentiation has been extensively studied, little is known about its role in the nervous system. In the present study, we analyzed SLURP-1 expression in the spinal cord of rats, as a number of studies suggest spinal nicotinic acetylcholine receptors are important modulators of pain transmission. We detected intense SLURP-1 immunoreactivity in the dorsal horn of the spinal cord, especially in lamina I and outer II. In dorsal root ganglia, SLURP-1 immunoreactivity was detected in small- to medium-sized neurons, where in situ hybridization also revealed the presence of SLURP-1 mRNA. Fluorescent labeling of SLURP-1 partially overlapped that of calcitonin-gene related peptide (CGRP) or substance P (SP) in both the spinal cord dorsal horn and glabrous skin, and electron microscopic analysis revealed colocalization of SLURP-1 with SP or CGRP, in large synaptic vesicles in terminals within the superficial layer of the spinal cord. Finally, sciatic nerve axotomy reduced levels of SLURP-1 immunoreactivity in parallel with that of SP and CGRP in the ipsilateral superficial dorsal horn. These findings suggest that SLURP-1 is expressed in a subset of primary peptidergic sensory neurons. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.