Histaminergic regulation of the neuroendocrine system: An analysis using microdialysis of the hypothalamus of conscious and freely moving rats.

近年来，利用免疫细胞化学方法在哺乳动物大脑中发现了组胺能神经元。组胺能神经元的细胞体定位于下丘脑后区结节乳头核，而其纤维几乎分布于大脑的所有区域。特别是在下丘脑核中，组胺能纤维密度最高，提示中枢组胺能系统参与神经内分泌系统的调节，但组胺能神经传递的详细神经化学机制及其生理作用尚不清楚。在脑功能中，下丘脑-垂体神经内分泌系统是唯一可以通过测量血浆激素水平来定量确定其功能的系统。在本研究中，我们应用微透析技术测定了下丘脑神经元组胺的动态变化，并试图将下丘脑的组胺释放与血液中几种激素的水平联系起来，以阐明组胺在神经内分泌系统中的生理作用。通过改善透析条件和检测灵敏度，我们可以检测下丘脑前部区组胺释放。通过几条神经药理学研究，我们也可以证实微透析测量的组胺是从神经末梢释放出来的。自由运动大鼠组胺释放具有明显的昼夜变化规律，在光照中期下降，在黑暗时期迅速上升并保持较高水平。在另一项实验中，长期服用特定的组胺合成抑制剂，血浆皮质酮和ACTH水平的昼夜变化消失。综上所述，利用微透析技术成功地监测了大鼠脑内源性神经元组胺的释放，该技术将为研究神经内分泌系统的组胺能调控提供依据。少

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 … More 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