REGULATION OF PITUITARY OPIATE PEPTIDE SECRETION

垂体阿片肽分泌的调节

• 批准号: 3402208
• 负责人: LINDA C SALAND
• 金额: $ 7.97万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402208
• 关键词: bioassay; corticotropin releasing factor; dopamine; electron microscopy; high performance liquid chromatography; hormone regulation /control mechanism; immunoperoxidase; melanocyte stimulating hormone; neurotoxins; neurotransmitter biosynthesis; opiate alkaloid; pituitary gland; radioimmunoassay; secretion; serotonin

This 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 neurotoxins, narcotic antagonist drugs, and selected opiate or hypothalamic peptides will be used in rodent pituitary glands in vitro. Since inhibition or stimulation of peptide secretion may also be affected by central nervous system mechanisms, an 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 radioimmunoassay 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 of pituitary peptide secretion, depending upon the agents' 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.

该应用概述了一项关于固有神经调节机制的研究 产生内源性鸦片和相关肽的细胞。 专业 要检验的假设是特定的抑制和刺激性 存在调节Opiomelanocortin肽分泌的机制。 到 检查抑制或刺激肽的假设 分泌直接发生在Opiomelananocortin细胞上，特异性 神经递质和神经毒素，麻醉拮抗剂药物，并选择 鸦片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也可能是 受中枢神经系统机制的影响，一种完整的体内啮齿动物 动物模型将用相同的神经毒素或麻醉品治疗 拮抗剂作为体外研究。 测量产出水平 体外或体内系统，生物测定或 用于刺激黑素细胞激素的放射免疫分子或放射免疫分子 对于β-内啡肽，将使用。 神经毒素在体内的特定作用 将通过高压液相色谱（HPLC）分析来确认 垂体和脑神经递质的。 垂体的放射免疫分子 将执行β-内啡肽的组织水平以比较 在血清中储存的肽水平。 最后， Opiomelanocortin细胞的细胞学和免疫组织化学研究，使用使用 将进行定性和定量方法进行评估 与对肽分析的相同的实验组内， 确定单个垂体分泌细胞的群体如何响应 抑制或刺激。 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 预防垂体肽分泌，具体取决于特工 特定神经递质的选择性。 体外和 关于啮齿动物垂体模型的体内研究将为 影响内源性鸦片释放和存储的特定机制 分子。