| Co-Investigator(Kenkyū-buntansha) |
TOHYAMA Masaya Department of Anatomy II, Osaka University Medical School, 医学部, 教授 (40028593)
FUKUI Hiroyuki Department of Pharmacology II, Osaka University Medical School, 医学部, 助教授 (90112052)
YAMATODANI Atsushi Department of Molecular Physiological Chemistry, Osaka University Medical School, 医学部, 助教授 (30116123)
WATANABE Takehiko Department of Pharmacology I, Tohoku University School of Medicine, 医学部, 教授 (70028356)
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| Research Abstract |
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
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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
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