ULTRASTRUCTURE AND CONTROL OF ENDORPHIN CELLS

内啡肽细胞的超微结构和控制

• 批准号: 3877456
• 负责人: LINDA C SALAND
• 金额: --
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3877456
• 关键词: Anura; catecholamines; concanavalin A; endorphins; high performance liquid chromatography; histochemistry /cytochemistry; hormone regulation /control mechanism; hypothalamus; immunochemistry; innervation; laboratory rat; ligands; neuroanatomy; neuropeptide receptor; neuropeptides; neurotoxins; neurotransmitters; opiate alkaloid; pituitary gland; radioimmunoassay; secretion; serotonin

The application outlines a study on intrinsic neuroregulatory mechanisms of cells which produce endogenous opiate and related peptides. The major hypothesis to be tested is that specific inhibitory and stimulatory mechanisms exist which regulate secretion of opiomelanocortin peptides. To examine the hypothesis of whether inhibition or stimulation of peptide secretion occurs directly on opiomelanocortin cells, specific neurotransmitters and neurotoxions, narcotic antagonist drugs, and selected opiate or hypothalamic peptides, will be used in rodent pituitary glands in vitro. Since inhibition or stimulation of peptides secretion may also be affected by central nervous system mechanisms, and intact in vivo rodent animal model will be treated with the same neurotoxins or narcotic antagonists as the in vitro studies. To measure the level of output of peptides from either the in vitro or in vivo systems, bioassay or radioimmunoassay for melanocyte- stimulating hormone, or radio-immunoassay for beta-endorphin, will be used. Specific effects of neurotoxins in vivo will be confirmed by high pressure liquid chromatographic (HPLC) analysis of pituitary and brain neurotransmitters. Radioimmunoassay for pituitary tissue levels of beta-endorphin will be performed in order to compare stored levels of peptide with released material in serum. Finally, cytologic and immunohistochemical studies of opiomelanocortin cells, using qualitative and quantitative methods for evaluation, will be performed within the same experimental groups as those assayed for peptides, to determine how individual groups of pituitary secretory cells respond to inhibition or stimulation. It is anticipated that neurotoxic agents or opiate antagonist drugs may have direct effects on stimulation or prevention peptide secretion, depending upon the agent's selectivity for a particular neurotransmitter. The use of in vitro and in vivo studies on the rodent pituitary gland model will provide support for specific mechanisms which affect release and storage of endogenous opiate molecules.

该应用程序概述了一项关于内在神经调节的研究 产生内源性鸦片和相关细胞的机制 肽。 要测试的主要假设是 存在调节的抑制和刺激机制 Opiomelanocortin肽的分泌。 检查假设 肽分泌的抑制或刺激是否发生 直接在Opiomelananocortin细胞上，特定的神经递质和 神经毒素，麻醉拮抗剂药物和选择的阿片类药物或 下丘脑肽将用于啮齿动物垂体 体外。 由于抑制或刺激肽分泌可能 也会受到中枢神经系统机制的影响，完整 体内啮齿动物模型将使用相同 神经毒素或麻醉拮抗剂作为体外研究。 到 测量从体外的肽的输出水平 或体内系统，用于黑素细胞的生物测定或放射免疫测定 刺激激素或用于β-内啡肽的无线电免疫测定法 被使用。 将确认神经毒素在体内的特定作用 通过高压液态色谱（HPLC）分析 垂体和脑神经递质。 放射免疫分子 将在 为了将肽的储存水平与释放的材料进行比较 在血清中。 最后，细胞学和免疫组织化学研究 Opiomelananocortin细胞，使用定性和定量方法 用于评估，将在同一实验中进行 作为对肽的分析的组，以确定个体如何 垂体分泌细胞组对抑制作用或 刺激。 预计神经毒性剂或鸦片 拮抗剂药物可能对刺激有直接影响或 预防肽分泌，具体取决于代理商的 特定神经递质的选择性。 体外使用 以及关于啮齿动物垂体模型的体内研究 为影响释放和的特定机制提供支持 内源性阿片类分子的存储。