AMINO ACID AND PEPTIDERGIC CONTROL OF SUPRAOPTIC NEURONS

后叶加压素和催产素，这两种激素在 维持血容量和渗透压，并在各种生殖 在哺乳动物中，由大细胞神经内分泌分泌 下丘脑-神经垂体系统（HNS）的细胞（MNCs）。 的目标 这里提出的研究是调查一些受体介导的 控制电活动和分泌活动的机制， 索马水平和轴突末端。 特别是，研究 集中在某些氨基酸和二肽的影响，包括 γ-氨基丁酸、谷氨酸、天冬氨酸、N-乙酰天冬氨酸（NAA），和 N-乙酰谷氨酸（NAAG）可能是许多神经递质， 包括HNS在内的CNS区域。 为了实现这些目标，全细胞电压和电流钳 技术将被用来研究受体的性质， 兴奋性和抑制性氨基酸，受体离子通道的性质 耦合和这些假定的神经递质对整体的影响， 跨国公司的电力活动。 记录将从分离的 成年大鼠视上核和新生大鼠培养的单个核细胞 视上神经元在研究受体机制的水平 下丘脑的细胞体 记录也将从孤立的 成年神经垂体的轴突终末，以研究轴突的机制 终端 成年神经元和轴突终末将从正常人获得。 大鼠和来自激素分泌增加两倍的大鼠 生理刺激：泌乳和脱水。 这些 电生理学研究将与对影响的研究相结合， 这些假定的神经递质可能控制分泌，也提供 深入了解化合物，这可能是治疗上有益的， 中风和癫痫，针对氨基酸介导的受体， 相关的离子通道，但与其他主要目标网站在中枢神经系统，可 影响这一重要的生理分泌系统。

The hormones vasopressin and oxytocin, which have crucial roles in maintenance of blood volume and osmolality and in various reproductive functions in mammals, are secreted by the magnocellular neuroendocrine cells (MNCs) of the hypothalamo-neurohypophysial system (HNS). The goal of the research proposed here is to investigate some of the receptor-mediated mechanisms that control electrical and secretory activities both at the level of the soma and at the axon terminal. In particular, the research is focussed upon the effects of certain amino acids and dipeptides, including gamma-aminobutyric acid, glutamate, aspartate, N-acetylaspartate (NAA), and N-acetylaspartatylglutamate (NAAG) which may be neurotransmitters in many areas of the CNS including the HNS. To achieve these objectives, whole-cell voltage and current clamp techniques will be used to investigate the nature of the receptors for excitatory and inhibitory amino acids, the nature of receptor-ion channel coupling and the effects of these putative neurotransmitters on the overall electrical activities of MNCs. Recording will be made from dissociated MNCs of the adult rat supraoptic nucleus and from cultured neonatal supraoptic neurons in studies of receptor mechanisms at the level of the cell body in the hypothalamus. Recordings will also be made from isolated axon terminals of the adult neurohypophysis to study mechanisms at the axon terminal. Adult neurons and axon terminals will be obtained from normal rats and from rats where hormone secretion is increased by two physiological stimuli: lactation and dehydration. These electrophysiological studies will be combined with studies on the effects of these putative neurotransmitters may control secretion and also provide insights into how compounds, which may be therapeutically beneficial in stroke and epilepsy, directed at amino acid-mediated receptors and associated ion channels, but with other prime target sites in the CNS, may affect this physiologically important hormone-secreting system.