Cellular basis for the effects of substance P in the periaqueductal gray and dorsal raphe nucleus
Cellular basis for the effects of substance P in the periaqueductal gray and dorsal raphe nucleus
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DOI：
10.1002/cne.10228
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发表时间：
2002-05-20
影响因子：
2.5
通讯作者：
Valentino, RJ
中科院分区：
文献类型：
--
作者：
Commons, KG;Valentino, RJ
已知P物质（SP）作用于脊髓上部位，影响疼痛敏感性并促进焦虑。SP的影响可以部分介导的行动，在导水管周围灰质（PAG）和中缝背核（DRN），毗邻中脑细胞群的战略定位，以影响伤害性感受和情绪。以前的研究表明，SP调节脑啡肽和5-羟色胺在这些脑区的神经传递。为了确定SP在PAG和DRN中的作用的机制，检查了SP的主要受体神经激肽I（NK 1）受体相对于其他神经递质标记物的分布。具有NK 1受体免疫标记的PAG神经元与含有脑啡肽的神经元相互交叉并接受接触。在DRN中，含有NK 1受体的树突选择性地分布于背内侧亚部。这些树突中的大多数（132/137; 96%）不含对降钙素合成酶色氨酸羟化酶的免疫反应性。相比之下，NK 1受体在PAG和DRN的神经元配置文件往往包含谷氨酸的免疫标记。光镜和电镜检查显示，48-65%的细胞体和树突与NK 1受体的双重免疫标记谷氨酸。这些数据表明，SP直接作用于PAG和DRN的多巴胺能神经元。在较小的程度上，含脑啡肽的神经元可以被靶向。通过这些作用，它可能随后影响含有脑啡肽和5-羟色胺的大量神经元的活动。该电路可以有助于，以及协调，对疼痛的感知和情绪的SP的影响。(C)2002年威利-利斯。Inc.
Substance P (SP) is known to act at supraspinal sites to influence pain sensitivity as well as to promote anxiety. The effects of SP could be mediated in part by actions in the periaqueductal gray (PAG) and the dorsal raphe nucleus (DRN), adjoining mesencephalic cell groups that are strategically positioned to influence both nociception and mood. Previous studies have indicated that SP regulates both enkephalin and serotonin neurotransmission in these brain regions. To determine the mechanism underlying the effects of SP in the PAG and DRN, the distribution of the principal receptor for SP, the neurokinin I (NK1) receptor, was examined with respect to other neurotransmitter markers. PAG neurons that had NK1 receptor immunolabeling were interdigitated With and received contacts from enkephalin-containing neurons. However, only a few (16/144; 111,c) neurons with NK1 receptor also contained enkephalin immunoreactivity after colchicine treatment, In the DRN, dendrites containing NK1 receptor were selectively distributed in the dorsomedial subdivision. The majority (132/137; 96%) of these dendrites did not contain immunoreactivity for the serotonin-synthesizing enzyme tryptophan hydroxylase. In contrast, neuronal profiles with NK1 receptor in both the PAG and the DRN often contained immunolabeling for glutamate. Light and electron microscopic examination revealed that 48-65% of cell bodies and dendrites with NK1 receptor were dually immunolabeled for glutamate. These data suggest that SP directly acts primarily on glutamatergic neurons in the PAG and DRN. To a lesser extent, enkephalin-containing neurons may be targeted. Through these actions, it may subsequently influence activity of larger populations of neurons containing enkephalin as well as serotonin. This circuitry could contribute to, as well as coordinate, effects of SP on pain perception and mood. (C) 2002 Wiley-Liss. Inc.