Pathophysiological significance of inducible histamine in the brain.

大脑中诱导型组胺的病理生理学意义。

• 批准号: 10670141
• 负责人: YAMATODANI Atsushi
• 金额: $ 1.28万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670141/
• 关键词: HISTAMINE; MICROGLIA; LIPOPOLYSACCHARIDE; CYTOKINE; HISTIDINE DECARBOXYLASE; MAST CELL; LIPTIN; INTERLEUKIN 1β; プロテインキナーゼC; インターロイキン1B; LPS

We previously reported that cells other than mast cells or neurons could synthesize histamine in response to lipopolysaccharide (LPS) or interleukin 1β in the rat brain. To identify the responsible cells, we examined histidine decarboxylase (HDC) activity and the expression of HDC mRNA in GMI6-3 mouse microglial cells. Both the activity and mRNA for HDC in GMI6-3 cells were induced by LPS treatment, and the induction was sensitive to calmodulin-dependent kinase II inhibitor, KN62. These findings indicate that microglia is a third cell type producing histamine in the brain.On the physiological significance of the brain histamine, we newly fond that (1) leptin injection significantly reduced food intake but not in H1-receptor knock out mice, (2) histamine release from the rat anterior hypothalamus was significantly increased by leptin, (3) leptin had no effect on histamine release in rats whose chorda tympani nerves were transected bilaterally. The findings clearly indicate that leptin, an anorectic hormone activates the histaminergic system by the peripheral signal inputs via the chorda tympani resulting in the suppression of food intake through histamine H1-receptors. Although the primary responsible cell on this effect is histaminergic neuronal cell, the microglial inducible histamine might have some anorectic effects through the above mentioned pathway in the course of inflammation.Finally, we are investigating the pathophysiological roles of the inducible histaine on blood-brain-barrier distraction

我们先前报道说，除肥大细胞或神经元以外的其他细胞可以响应大鼠脑中的脂多糖（LPS）或白介素1β而合成组胺。为了鉴定负责细胞，我们检查了组氨酸脱羧酶（HDC）活性和HDC mRNA在GMI6-3小鼠小胶质细胞中的表达。 HDC在GMI6-3细胞中的活性和mRNA均通过LPS处理诱导，诱导对钙调蛋白依赖性激酶II抑制剂KN62敏感。这些发现表明，小胶质细胞是大脑中产生组胺的第三种细胞类型。在脑组胺的物理意义上，我们刚喜欢（1）（1）瘦素注射显着降低食物摄入量，但在H1受体中却没有敲开小鼠，（2）由大鼠内侧的leptin释放出（2）leptin（3）leptin的效果（3），leptin的作用显着（3）。组胺能神经元细胞，小胶质细胞诱导组胺在炎症过程中可能通过上述途径具有一些厌食作用。在本文中，我们正在研究诱导型组织对血液脑伴侣伴侣的病理生理作用

项目成果

Y.Katoh,M.Niimi,Y.Yamamoto,H.Takemori,M.Sawada,A.Yamatodani: "Histamine production by cultured micrglial cells."Neurosci.Lett.. (in press). (2001)

Y.Katoh、M.Niimi、Y.Yamamoto、H.Takemori、M.Sawada、A.Yamatodani：“培养的小胶质细胞产生组胺。”Neurosci.Lett..（出版中）。

T.Morimoto,Y.Yamamoto,A.Yamatodani: "Leptin facilitates histamine release from the hypothalamus in rats"Brain Res.. 868(2). 367-369 (2000)

T.Morimoto、Y.Yamamoto、A.Yamatodani：“瘦素促进大鼠下丘脑释放组胺”Brain Res.. 868(2)。

J.Chen,O.Ikeda,T.Hatasa,A.Kitajima,M.Miyake,A.Yamatodani: "Oxidation of NO mediated by water-soluble iron porphyrin"Electrochem.Commun.. 1. 274-277 (1999)

J.Chen,O.Ikeda,T.Hatasa,A.Kitajima,M.Miyake,A.Yamatodani：“水溶性铁卟啉介导的 NO 氧化”Electrochem.Commun.. 1. 274-277 (1999)

S.Harusawa,T.Imazu,S.Takashima,L.Araki,H.Ohishi,T.Kurihara,Y.Yamamoto,A.Yamatodani: "Synthesis of Imifuramine and its stereoisomers exhibiting histamine H3-agonistic activity"Tetrahedron Lett.. 40(13). 2561-2564 (1999)

S.Harusawa、T.Imazu、S.Takashima、L.Araki、H.Ohishi、T.Kurihara、Y.Yamamoto、A.Yamatodani：“咪呋明及其立体异构体的合成，表现出组胺 H3 激动活性”Tetrahedron Lett..

T.Morimoto,Y.Yamamoto,J.I.Mobarakeh,K.Yanai,T.Watanabe,A.Yamatodani: "Involvement of the histaminergic system in leptin-induced suppression of food intake"Physiol.Behav.. 67(5). 679-683 (1999)

T.Morimoto，Y.Yamamoto，J.I.Mobarakeh，K.Yanai，T.Watanabe，A.Yamatodani：“组胺能系统参与瘦素诱导的食物摄入抑制”Physiol.Behav.. 67（5）。