BRAIN AMINES--REGULATION AND FUNCTION

本项目的主要目标是：（1）检查形成， 脑内生物胺的释放、代谢和处置 给药后的变化或毒素诱导的模型 人类疾病;（2）确定生物胺的生理作用， 调解对压力的反应;（3）开发可以 适用于人脑生物胺代谢的研究。 体内微透析已被用于监测单胺的水平， 它们的代谢物在细胞外液中的不同区域的 下丘脑和基底神经节。 受体和转运蛋白 在体外使用来自大脑不同区域的细胞进行了检查： 从下丘脑培养的细胞系;和在胃肠道中 道之前和之后制动（IMO）的压力。 在IMO期间，NE释放到细胞外液（ECF）中的区域 下丘脑和杏仁核明显增加。 经过反复 IMO的间隔，NE合成和周转指数， 与几个地区的基础递质释放有关。 育亨宾， α 2-肾上腺素受体拮抗剂，增强NE的释放，推测是通过 阻断突触前抑制释放。 这种影响似乎是 在幼年自发性高血压大鼠中增加， 慢性皮质醇治疗后减弱。 MAO-B的抑制，但 而不是MAO-A，在一段时间内逐渐升高NE的ECF水平， 天，符合MAO临床疗效的逐渐显现 抑制剂的 MAO-A的抑制增强了L-多巴诱导的 纹状体ECF中的多巴胺水平 使用一种新的方法， 将试剂直接引入微透析尖端区域 探针，甘氨酸被证明可以刺激多巴胺从 纹状体中的剂量依赖性，士的宁敏感的方式。 在 下丘脑神经元，在培养和体内，似乎有一个新的 地昔帕明敏感的NE转运体，可能负责 使儿茶酚胺失活。 微透析研究将扩大到包括氨基酸和肽 将检查神经递质、额外的应激源和激素， 分子生物学技术将被应用于追求的作用， 在应激过程中改变了中枢儿茶酚胺能功能， SHR大鼠高血压的发展，并表征新的NE 运输机

The main objectives of this project are to: (1) examine formation, release, metabolism and disposition of brain biogenic amines and their alterations after administration of drugs or toxin-induced models of human disease; (2) determine the physiologic role of biogenic amines in mediating responses to stress; and (3) develop methods that can be adapted to study of brain biogenic amine metabolism in humans. In vivo microdialysis has been used to monitor levels of monoamines and their metabolites in extracellular fluid in various regions of the hypothalamus and in the basal ganglia. Receptors and transporters have been examined in vitro using cells from different regions of brain: in cell lines cultured from the hypothalamus; and in the gastrointestinal tract before and after immobilization (IMO) stress. During IMO, release of NE into th extracellular fluid (ECF) in regions of the hypothalamus and the amygdala is increased markedly. After repeated intervals of IMO, indices of NE synthesis and turnover that were not correlated with basal transmitter release in several areas. Yohimbine, an alpha2-adrenoceptor antagonist, enhances release of NE, presumably by blocking presynaptic inhibition of release. This effect appears to be augmented in juvenile spontaneously hypertensive rats and to be attenuated after chronic cortisol treatment. Inhibition of MAO-B, but not MAO-A, gradually elevates ECF level of NE over a time interval of days, consistent with the gradual appearance of clinical efficacy of MAO inhibitors. Inhibition of MAO-A enhances the L-dopa-induced elevation of levels of dopamine in the ECF of the striatum. Using a new method for introducing agents directly into the region of the tip of a microdialysis probe, glycine was shown to stimulate release of dopamine from the striatum in a dose-dependent, strychnine-sensitive manner. In hypothalamic neurons, in culture and in vivo, there appears to be a novel desipramine-sensitive NE transporter which may be responsible for inactivation of the catecholamine. Microdialysis studies will be expanded to include amino acid and peptide neurotransmitters, additional stressors and hormones will be examined and molecular biology techniques will be applied to pursue the role of altered central catecholaminergic function in stress, during the development of hypertension in the SHR rat, and to characterize novel NE transporters.