Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes

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• 作者：Trevor J. Bushell ; Robin Plevin ; Stuart Cobb and Andrew J. Irving
• 关键词：Hippocampus ; Proteinase-activated receptor ; Calcium ; Signalling ; Expression
• 刊名：Neuropharmacology
• 出版年：2006
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：May 2006
• 卷：50
• 期：6
• 页码：714-725
• 文件大小：2904 K

摘要

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.