Expression of mRNA for four subtypes of the proteinase-activated receptor in rat dorsal root ganglia

Expression of mRNA for four subtypes of the proteinase-activated receptor in rat dorsal root ganglia
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DOI:
10.1016/j.brainres.2005.02.018
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发表时间:
2005-04
期刊:
影响因子:
2.9
通讯作者:
Wan-Jun Zhu;H. Yamanaka;K. Obata;Yi Dai;Kimiko Kobayashi;T. Kozai;A. Tokunaga;K. Noguchi
Wan-Jun Zhu;H. Yamanaka;K. Obata;Yi Dai;Kimiko Kobayashi;T. Kozai;A. Tokunaga;K. Noguchi
中科院分区:
医学3区
文献类型:
--
作者:
Wan-Jun Zhu;H. Yamanaka;K. Obata;Yi Dai;Kimiko Kobayashi;T. Kozai;A. Tokunaga;K. Noguchi

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蛋白水解酶激活受体(PARs)是G蛋白偶联受体超家族的成员,通过胞外丝氨酸蛋白酶的蛋白分解活性启动细胞内信号传导。这个家族中的三个成员(PAR-1、PAR-3和PAR-4)被认为是凝血酶受体,而PAR-2被胰酶和类胰蛋白酶激活。最近,PAR-2信号的激活被认为是介导伤害性感受器外周敏化的促炎因子。外周PAR-1的激活也被认为是参与肽释放的炎症的神经源性介质。在这里,我们用放射性同位素标记的原位杂交组织化学方法研究了这四个PARS成员在成年大鼠背根神经节(DRG)中的表达。我们检测了DRG中所有亚型PARs的mRNA。组织学分析揭示了PARs的特殊表达模式。PAR-1、PAR-2和PAR-3mRNA分别在29.0±4.0%、16.0±3.2%和40.9±1.3%的DRG神经元中表达。而PAR-4mRNA主要表达于非神经细胞。核因子-200和降钙素基因相关肽(CGRP)对PARs的双重标记研究也表明PARs在有髓神经元或伤害性神经元中有明显的表达。本研究显示了DRG中pars mRNA的精确表达模式,表明DRG中的细胞可以受到不同类型的蛋白水解酶激活受体的调节。
Proteinase-activated receptors (PARs) are members of the superfamily of G-protein coupled receptors that initiate intracellular signaling by the proteolytic activity of extracellular serine proteases. Three member of this family (PAR-1, PAR-3, and PAR-4) are considered thrombin receptors, whereas PAR-2 is activated by trypsin and tryptase. Recently, activation of PAR-2 signal was identified as a pro-inflammatory factor that mediates peripheral sensitization of nociceptors. Activation of PAR-1 in the periphery is also considered to be a neurogenic mediator of inflammation that is involved in peptide release. Here, we investigated the expression of these four members of PARs in the adult rat dorsal root ganglia (DRG) using radioisotope-labeled in situ hybridization histochemistry. We detected mRNA for all subtypes of PARs in the DRG. Histological analysis revealed the specific expression patterns of the PARs. PAR-1, PAR-2, and PAR-3 mRNA was expressed in 29.0 ± 4.0%, 16.0 ± 3.2%, and 40.9 ± 1.3% of DRG neurons, respectively. In contrast, PAR-4 mRNA was mainly observed in non-neuronal cells. A double-labeling study of PARs with NF-200 and alpha calcitonin gene-related peptide (CGRP) also revealed the distinctive expression of PARs mRNA in myelinated or nociceptive neurons. This study shows the precise expression pattern of PARs mRNA in the DRG and indicates that the cells in DRG can receive modulation with different types of proteinase-activated receptors.