Hegarty Deborah M, Mitchell Jennifer L, Swanson Kristin C, Aicher Sue A
Oregon Health and Science University, Neurological Sciences Institute, Beaverton, OR 97006, USA.
Brain Res. 2007 Dec 12;1184:149-59. doi: 10.1016/j.brainres.2007.09.070. Epub 2007 Oct 4.
Kainate receptors (KARs) are involved in the modulation and transmission of nociceptive information from peripheral afferents to neurons in the spinal cord and trigeminal dorsal horns. KARs are found at both pre- and postsynaptic sites in the dorsal horn. We hypothesized that KARs and Substance P (SP), a modulatory neuropeptide that is used as a marker of nociceptive afferents, have a complex interactive relationship. To determine the cellular relationship and connectivity between KARs and SP afferents, we used electron microscopic dual immunocytochemical analysis to examine the ultrastructural localization of KAR subunits GluR5, 6 and 7 (GluR5,6,7) in relation to SP within laminae I and II in the rat trigeminal dorsal horn. KARs were distributed both postsynaptically in dendrites and somata (51% of GluR5,6,7 immunoreactive (-ir) profiles) and presynaptically in axons and axon terminals (45%). We also found GluR5,6,7-ir glial profiles (5%). The majority of SP-ir profiles were presynaptic axons and axon terminals. SP-ir dendritic profiles were rare, yet 23% contained GluR5,6,7 immunoreactivity. GluR5,6,7 and SP were also colocalized at presynaptic sites (18% of GluR5,6,7-ir axons and axon terminals contained SP; while 11% of SP-ir axons and axon terminals contained GluR5,6,7). The most common interaction between KARs and SP we observed was GluR5,6,7-ir dendrites contacted by SP-ir axon terminals; 54% of the dendritic targets of SP-ir axon terminals were GluR5,6,7-ir. These results provide anatomical evidence that KARs primarily mediate nociceptive transmission postsynaptic to SP-containing afferents and may also modulate the presynaptic release of SP and glutamate in trigeminal dorsal horn.
海人藻酸受体（KARs）参与伤害性信息从外周传入神经到脊髓和三叉神经背角神经元的调制与传递。在背角的突触前和突触后位点均发现有KARs。我们推测KARs与P物质（SP）存在复杂的交互关系，P物质是一种用作伤害性传入神经标记物的调制性神经肽。为确定KARs与SP传入神经之间的细胞关系和连接性，我们采用电子显微镜双免疫细胞化学分析，研究大鼠三叉神经背角I层和II层中KAR亚基GluR5、6和7（GluR5,6,7）相对于SP的超微结构定位。KARs分布于突触后树突和胞体（占GluR5,6,7免疫反应性（-ir）轮廓的51%）以及突触前轴突和轴突终末（占45%）。我们还发现了GluR5,6,7-ir神经胶质轮廓（占5%）。大多数SP-ir轮廓为突触前轴突和轴突终末。SP-ir树突轮廓很少见，但23%含有GluR5,6,7免疫反应性。GluR5,6,7和SP也共定位于突触前位点（18%的GluR5,6,7-ir轴突和轴突终末含有SP；而11%的SP-ir轴突和轴突终末含有GluR5,6,7）。我们观察到的KARs与SP之间最常见的相互作用是SP-ir轴突终末与GluR5,6,7-ir树突接触；SP-ir轴突终末的树突靶点中有54%是GluR5,6,7-ir。这些结果提供了解剖学证据，表明KARs主要介导含SP传入神经突触后的伤害性传递，并且可能还调节三叉神经背角中SP和谷氨酸的突触前释放。
