| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Recently, the histaminergic neurons have been identified in mammalian brains by immunocytochemical methods. The cell bodies of the histaminergic neurons are localized in the tuberomammillary nucleus in the posterior hypothalamic region, while the fibers are found in almost all regions of the brain. Especially in the hypothalamic nuclei, the highest density of the histaminergic fibers were found, suggesting the involvement of the central histaminergic system in the regulation of neuroendocrine system, However, detailed neurochemical mechanism of the histaminergic neurotransmission and its physiological roles are still not clear.
Among the brain functions, the hypothalamo-hypophyseal neuroendocrine system is the only one whose function can be determined quantitatively by measurement of the plasma levels of the hormones. In this study, we applied the microdialysis technique to determine the dynamics of the neuronal histamine in the hypothalamus, and we tried to correlate the histamine rele
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ase in the hypothalamus and the levels of several hormones in blood to elucidate the physiological roles of histamine in the neuroendocrine system.
By improving the dialysis conditions and the assay sensitivity, we could detect histamine release from anterior hypothalamic area. By several lines of neuropharmacological studies, we could also confirm that histamine measured by the microdialysis was released from the nerve terminals. In the freely moving rats, the histamine release was found to show a clear circadian variation, decreasing during the mid-light period, then rapidly increasing and keeping high levels during the dark period. In another experiment, circadian variation of the plasma levels of corticosterone and ACTH was disappeared by chronic administration of the specific inhibitor of histamine synthesis. In conclusion, the release of endogenous neuronal histamine in rat brain was successfully monitored using a new technique of microdialysis, and this technique will be useful to investigate the histaminergic regulation of the neuroendocrine system. Less
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