Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes
Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes
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DOI：
10.1016/j.neuropharm.2005.11.024
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发表时间：
2006-05-01
影响因子：
4.7
通讯作者：
Irving, Andrew J.
中科院分区：
文献类型：
--
作者：
Bushell, Trevor J.;Plevin, Robin;Irving, Andrew J.
蛋白酶激活受体（PARs 1 -4）是丝氨酸蛋白酶对细胞作用的分子基础。在本研究中，我们研究了PAR 2信号，表达和脱敏使用培养和急性切片制备。胰蛋白酶，SLIGRL和2f-LIGKV-OH，PAR 2的激动剂，通过激活磷脂酶C/IP 3途径诱导神经元和星形胶质细胞细胞内Ca 2+水平的瞬时增加。此外，单次应用胰蛋白酶，而不是SLIGRL或2f-LIGKV-OH，导致PAR 2应答的延长脱敏。在培养物和急性切片内的神经元（谷氨酸能和GABA能）和星形胶质细胞中观察到PAR 2免疫反应性，在神经元胞体和近端树突中具有显著标记。在功能上，表现出最高水平的PAR 2标记的培养的神经元，也表现出最大的Ca 2+信号后PAR 2激活。鉴于海马突触可塑性和神经变性中Ca 2+信号传导的重要性，PAR 2可能在这些过程中发挥关键的调节作用。(c)2005爱思唯尔有限公司保留所有权利。
Proteinase-activated receptors (PARs1-4) have recently been identified as the molecular entity underlying the cellular effects of serine proteinases. In the present study we have investigated PAR2 signalling, expression and desensitization using cultured and acute slice preparations. Trypsin, SLIGRL and 2f-LIGKV-OH, agonists for PAR2, induced a transient increase in intracellular Ca2+ levels in both neurons and astrocytes, via activation of the phospholipase C/IP3 pathway. Furthermore, a single application of trypsin, but not SLIGRL nor 2f-LIGKV-OH, leads to prolonged desensitization of PAR2 responses. PAR2 immunoreactivity was observed in neurons (glutamatergic and GABAergic) and astrocytes within cultures and acute slices, with prominent labelling in neuronal somata and proximal dendrites. Functionally, cultured neurons which exhibited the highest levels of PAR2 labelling, also exhibited the largest Ca2+ signals upon PAR2 activation. Given the importance of Ca2+ signalling in hippocampal synaptic plasticity and neurodegeneration, PAR2 may play a key modulatory role in these processes. (c) 2005 Elsevier Ltd. All rights reserved.