Investigation on signal transduction pathways after H₁ receptor activated by histamine in C6 glioma cells: Involvement of phosphatidylinositol and arachidonic acid metabolisms

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• 作者：Chin-Lu Tseng^a ; Jiann-Wu Wei^b ; ^{jiann-wu.wei@ricerca.com}
• 关键词：arachidonic acid ; C6 glioma cells ; glycerophosphoric-inositol ; histamine H1 receptor ; inositol 4-phosphate
• 刊名：Journal of the Chinese Medical Association
• 出版年：2012
• 期刊代码：210_17264901
• 类别：med
• 出版时间：April, 2012
• 卷：75
• 期：4
• 页码：143-150
• 文件大小：641 K

摘要

4 class="h4">Background4>Information related to histamine-induced cellular responses in C6 glioma cells through second messenger pathways has not been fully studied, especially the involvement of arachidonic acid (AA) metabolism. In addition, specific labeled ligand binding to histamine receptor sites still needs to be clarified.4 class="h4">Methods4>

Labeled mepyramine ligand was used to study its binding sites; [³H] inositol was used to detect inositol 4-phosphate (IP₁) formation, and fura-2/AM was used to detect intracellular free calcium ion ([Ca²⁺]i) level activated by the phosphatidylinositol-phospholipase C (PI-PLC) pathway. Also, labeled AA was used to detect the metabolism of AA and its metabolites release via the activation of phospholipase A2 in the presence of histamine.4 class="h4">Results4>

C6 glioma cells incubated with histamine in the presence of 10聽mM LiCl for 60 minutes induced an increase of IP₁ and glycerophosphoric-inositol (GPI) accumulation. In addition, histamine caused an increase of extracellular AA with its metabolite release, eliciting a transient and sustained increase of free [Ca²⁺]i. The sustained increase of [Ca²⁺]i was almost or completely blocked by La³⁺ and excess ethylene diamine tetraacetic acid. The calcium ion influx associated with the sustained phase required the presence of histamine on the receptor sites, and could be blocked by a H₁ antagonist, chlorpheniramine.4 class="h4">Conclusion4>

C6 glioma cells possess histamine H₁ receptors that have affinity towards [³H]mepyramine binding, and are coupled to PI-PLC to generate inositol phosphates and to increase [Ca²⁺]i, and they are coupled to phospholipase A2 (PLA2) to generate GPI and AA with its metabolite release. The transient increase in [Ca²⁺]i can be attributed to Ca²⁺ release from intracellular stores, whereas the sustained increase in [Ca²⁺]i is due to influx of extracellular calcium ions. The sustained increase in [Ca²⁺]i plays a role in the activation of histamine receptor-coupled PLA2.