Physiological Roles of Histamine in the Brain as a Neurotransmitter

组胺作为神经递质在大脑中的生理作用

• 批准号: 60440030
• 负责人: WADA Hiroshi
• 金额: $ 19.01万
• 依托单位: Osaka University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60440030/
• 关键词: Rat; Histamine; Central Nervous System; Neuroendocrine system; Circadian Rhythm; Neuromodulator; H1-Receptor; 神経内分泌; 動揺病; 視床下部灌流; 【H_1】-受容体の精製; ヒスタミン; 睡眠-覚醒リズム; コルチコステロン; 視床下部潅流; 【H_1】受容体

Histamine as a neurotransmitter or a neuromodulator in the mammalian brain has been postulated on the basis of biochemical, pharmacological and neurophysiological studies. In 1982, we showed the clear evidence for the presence of non-mast-cell histamine in the brain by using a genetically mast-cell-deficient mouse,and estimated the turnover rate of the neuronal histamine as about 60 min. Recently, we demonstrated the central histaminergic neuron system in rats using an antibody raised against histidine decarboxylase, the sole enzyme responsible for the histamine synthesis, as a marker. The immunoreactive cell bodies were found to be confined in the magnocellular nuclei in the posterior hypothalamic region, and sent their fibers throughout the brain.In this project, we examined the distribution of the histaminergic fibers in detail. The highest concentrations of the immunoreactive fibers were found in the hypothalamic nuclei and medial forebrain bundle, and high to moderate densities of … More the fibers were found in the thalamic nuclei, cerebral cortex, septum, basal ganglia, amygdaloid complex and dorsal part of the brain system. From this distribution of the histaminergic system, it is plausible to assume that the brain histamine might be involved in various important physiological roles, especially in modulate several hypothalamic functions. Thus we studied the effect of neural histamine depletion on the neuroendocrine functions by the administration of alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, and found that chronic administration of FMH to rats diminished the clear diurnal variation of plasma corticosterone, the elevation of plasma ACTH after bilateral adrenalectomy and the elevation of plasma vasopressin after hypertonic saline injection without affecting their basal plasma levels. We also found several evidences that the histaminergic neuron system was involved in the regulation of sleep-wakefulness cycle, feeding behavior and thermoregulation.All these results indicate that the histaminergic neuron system does not have independent and/or separate functions in the central nervous system, but act as a king of neuromodulator in controlling the brain function as a whole. In addition, we performed solubilization and purification of histamine H1-receptor inthis project. Less

项目成果

N.Inagaki: Brain Res.418. 388-391 (1987)

N.Inagaki：大脑研究 418。

N.Inagaki: "The histaminergic innervation of the mesencephalic nucleus of the trigeminal nerve in rat brain: a light and electron microscopical study." Brain Res.418. 388-391 (1987)

N.Inagaki：“大鼠大脑中三叉神经中脑核的组胺能神经支配：光和电子显微镜研究。”

N.P.Wang: "Determination of the molecular size of the hepatic H_1-receptor by target size analysis." Biochem.Biophys.Res.Commun.137. 593-598 (1986)

N.P.Wang：“通过目标尺寸分析确定肝 H_1 受体的分子尺寸。”

R.Cacabelos: Neuroendocrinology. (1987)

R.Cacabelos：神经内分泌学。

H.Fukui: "Solubilization, characterization and partical purification of ^3H-mepyramine-binding protein, a possible histamine H_1-receptor, from rat liver membrane." Jpn.J.Pharmacol.46. 127-139 (1988)

H.Fukui：“^3H-美吡拉明结合蛋白（一种可能的组胺 H_1 受体）从大鼠肝膜中的溶解、表征和颗粒纯化。”