Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii

Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii
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DOI:
10.1016/j.neuroscience.2008.03.078
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发表时间:
2008-06-23
期刊:
影响因子:
3.3
通讯作者:
Talman, W. T.
Talman, W. T.
中科院分区:
医学3区
文献类型:
--
作者:
Lin, L. H.;Taktakishvili, O. M.;Talman, W. T.

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P物质(SP)和谷氨酸参与孤立束核(NTS)的心血管调节。我们早期的研究表明,作用于神经激肽1 (NK1)受体的SP不是一种压力反射递质,而谷氨酸是。另一方面,我们最近的研究表明,表达NK1受体的NTS神经元的丧失会导致压力反射反应的丧失和血压不稳定性的增加。此外,研究表明SP可能在NTS中与谷氨酸相互作用。在这项研究中,我们试图验证NK1受体与谷氨酸受体共定位的假设,无论是n -甲基- d -天冬氨酸(NMDA)受体还是AMPA受体,还是两者都在NTS中。我们在大鼠NTS中对NK1受体和n -甲基- d -天冬氨酸受体亚基1 (NMDAR1)或AMPA特异性谷氨酸受体亚基2 (GluR2)进行了双标记免疫荧光染色。由于含有谷氨酸囊泡转运蛋白2 (VGLUT2)的纤维在NTS心血管传入纤维终止的部分突出,我们还对NK1受体和VGLUT2进行了双标记免疫荧光染色。共聚焦显微镜图像显示,NK1受体-免疫反应性(IR)和NMDAR1-IR共定位在许多NTS亚核的相同神经元中。几乎所有NK1受体- ir阳性的NTS神经元也含有NMDAR1-IR,但只有53.4% ~ 74.8%的NMDAR1-IR阳性神经元含有NK1受体- ir。NK1受体- ir和GluR2-IR也在NTS亚核的许多神经元中共定位。大多数NK1受体- ir阳性的NTS神经元也含有GluR2-IR,但只有45.8%至73.9%的GluR2-IR阳性NTS神经元含有NK1受体- ir。我们的研究结果还表明,VGLUT2-IR标记的纤维与NK1受体- ir标记的纤维和神经元密切相关。这些数据支持了我们的假设,为谷氨酸和SP相互作用提供了一个解剖学框架,并可能解释了当NTS神经元(可以对谷氨酸和SP做出反应)被杀死时,压力反射的丧失。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
Substance P (SP) and glutamate are implicated in cardiovascular regulation by the nucleus tractus solitarii (NTS). Our earlier studies suggest that SP, which acts at neurokinin 1 (NK1) receptors, is not a baroreflex transmitter while glutamate is. On the other hand, our recent studies showed that loss of NTS neurons expressing NK1 receptors leads to loss of baroreflex responses and increased blood pressure lability. Furthermore, studies have suggested that SP may interact with glutamate in the NTS. In this study, we sought to test the hypothesis that NK1 receptors colocalize with glutamate receptors, either N-methyl-D-aspartate (NMDA) receptors or AMPA receptors or both in the NTS. We performed double-label immunofluorescent staining for NK1 receptors and either N-methyl-D-aspartate receptor subunit 1 (NMDAR1) or AMPA specific glutamate receptor subunit 2 (GluR2) in the rat NTS. Because vesicular glutamate transporter 2 (VGLUT2) containing fibers are prominent in portions of the NTS where cardiovascular afferent fibers terminate, we also performed double-label immunofluorescent staining for NK1 receptors and VGLUT2. Confocal microscopic images showed that NK1 receptors-immunoreactivity (IR) and NMDAR1-IR colocalized in the same neurons in many NTS subnuclei. Almost all NTS neurons positive for NK1 receptor-IR also contained NMDAR1-IR, but only 53.4% to 74.8% of NMDAR1-IR positive neurons contained NK1 receptors-IR. NK1 receptor-IR and GluR2-IR also colocalized in many neurons in NTS subnuclei. A majority of NK1 receptor-IR positive NTS neurons also contained GluR2-IR, but only 45.8% to 73.9% of GluR2-IR positive NTS neurons contained NK1 receptors-IR. Our results also showed that fibers labeled for VGLUT2-IR were in close apposition to fibers and neurons labeled for NK1 receptor-IR. The data support our hypothesis, provide an anatomical framework for glutamate and SP interactions, and may explain the loss of baroreflexes when NTS neurons, which could respond to glutamate as well as SP, are killed. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.