Activation of histamine H1-receptor enhances neurotrophic factor secretion from cultured astrocytes
Activation of histamine H1-receptor enhances neurotrophic factor secretion from cultured astrocytes
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DOI：
10.1007/s00011-004-1247-3
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发表时间：
2004-05-01
影响因子：
6.7
通讯作者：
Carman-Krzan, M
中科院分区：
文献类型：
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作者：
Lipnik-Stangelj, M;Carman-Krzan, M
目的：组胺刺激培养星形胶质细胞分泌神经生长因子（NGF）。组胺h -1受体拮抗剂完全阻断其作用。在本研究中，我们确定了组胺受体亚型参与这一过程。材料和方法：采用放射配体结合法测定原代培养新生大鼠皮质星形胶质细胞中存在组胺H-1和h -2受体。用组胺H-1-、H-2-和H-3/ h -4受体配体和高选择性蛋白激酶C （PKC）抑制剂影响培养星形胶质细胞NGF的分泌。将NGF释放到培养基中，用NGF- elisa法测定。结果：组胺h -1受体激动剂（组胺，选择的组蛋白）以浓度依赖的方式增加培养星形胶质细胞的NGF分泌。h -1受体拮抗剂/逆激动剂（甲皮拉米、triprolidine）和PKC抑制剂完全阻断组胺的作用。组胺H-2和h -3受体激动剂对NGF分泌无显著促进作用。此外，H-2和H-3/ h -4受体拮抗剂不会减少组胺刺激的NGF释放。结论：组胺h -1受体和PKC参与了组胺刺激星形胶质细胞分泌NGF的信号转导途径。
Objective:Histamine stimulates nerve growth factor (NGF) secretion from cultured astrocytes. Histamine H-1-receptor antagonists completely block its effect. In the present study, we determined the involvement of histamine-receptor subtypes in this process.Materials and methods:Radioligand-binding assay was used to establish the presence of histamine H-1- and H-2-receptors on new-born rat cortical astrocytes in primary culture. Histamine H-1-, H-2- and H-3/H-4-receptor ligands, and highly selective protein kinase C (PKC) inhibitor were used to influence NGF secretion from cultured astrocytes. NGF, released into the culture medium, was measured by NGF-ELISA.Results:Histamine H-1-receptor agonists (histamine, selected histaprodifens) increased the secretion of NGF from cultured astrocytes in a concentration-dependent manner. H-1-receptor antagonists/inverse agonists (mepyramine, triprolidine) and PKC inhibitor completely blocked the effect of histamine. Histamine H-2- and H-3-receptor agonists did not enhance NGF secretion significantly. In addition, H-2- and H-3/H-4-receptor antagonists did not diminish histamine-stimulated NGF release.Conclusions:Our results indicate that histamine H-1-receptor and PKC are involved in the signal transduction pathway, responsible for histamine-stimulated NGF secretion from cultured astrocytes.