REGULATION OF SECRETION OF POMO PEPTIDES IN BRAIN

脑内 POMO 肽分泌的调节

• 批准号: 3406609
• 负责人: LEONARD P KAPCALA
• 金额: $ 18.55万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406609
• 关键词: acetylcholine; adrenocorticotropic hormone; brain cell; brain metabolism; corticotropin releasing factor; dopamine; drug interactions; embryo /fetus; gamma aminobutyrate; glucocorticoids; high performance liquid chromatography; hormone regulation /control mechanism; hypothalamus; medulla oblongata; melanocyte stimulating hormone; molecular shape; neural information processing; neuroanatomy; neurochemistry; neuropharmacology; norepinephrine; pituitary gland; proopiomelanocortin; prosencephalon; radioimmunoassay; secretion; serotonin; tissue /cell culture; vasopressins

Various, behavioral, biochemical and neuromodulatory effects have been produced in brain by ACTH, alpha-MSH, beta- endorphin, and related peptides derived from processing of their precursor, pro-opiomelanocortin (POMC), which is synthesized by neurons. Despite a variety of in vivo studies investigating different variables on brain levels of POMC-related peptides, a clear conception of the physiological regulation of POMC peptides in brain remains to be established. To understand the regulation of brain POMC peptides by delineating potential physiological regulators, a variety of substances will be studied for effects on altering secretion of POMC peptides from brain cells. We will test hypotheses that brain secretion of POMC peptides is: 1) regulated by neurotransmitters modifying neuronal functions, by substances modifying brain POMC peptides in vivo, and by substances (CRF, glucocorticoids, beta- endorphin) which regulate secretion of pituitary POMC peptides; 2) regulated differently in hypothalamic and extrahypothalamic brain; 3) non-coordinated; 4) dependent on neuroanatomical relationships; 5) independent of cellular content of POMC peptides. We will use in vitro models to study secretion which is difficult to study in vivo. Regulatory effects of classical neurotransmitters on secretion will be evaluated in a static system of dissociated fetal rat hypothalamic cells by measuring (RIA) POMC peptides (ACTH, alpha-MSH, beta-endorphin) and comparing results to those in perifusion systems of cells and explants. Pharmacological antagonism of neurotransmitter- altered secretion will be assessed. Neurotransmitter effects on POMC peptide secretion will be further evaluated in cells from extrahypothalamic forebrain and medulla oblongata. Effects of other regulatory candidates will subsequently be studied and compared in hypothalamic and extrahypothalamic cells. Effects of chronic exposure of selected substances on secretion and content of POMC peptides will also be assessed. Molecular forms of POMC peptides will be characterized and molar relationships analyzed to indicate if regulation of secretion is coordinated or non-coordinated. Completing this project will help understand the physiological regulation of secretion of POMC peptides, could help understand brain regulation of synthesis and processing of POMC peptides, and could lead to studies elucidating their CNS function and models indicating whether alterations in regulation of POMC peptide metabolism produce or exacerbate CNS disorders (schizophrenia, SIDS, seizures, infantile spasms).

各种行为、生化和神经调节效应 在大脑中由ACTH、α-MSH、β-MSH- 内啡肽，以及从其加工过程中衍生的相关多肽 前体，前阿片黑素皮质素(POMC)，合成 由神经元控制。尽管各种体内研究都在研究 不同变量对大脑POMC相关多肽水平的影响 对POMC生理调节的清晰认识 脑内的多肽仍有待证实。要了解 通过描绘电位调节脑POMC多肽 生理调节剂，多种物质将被研究 对改变脑内POMC多肽分泌的影响 细胞。我们将检验POMC大脑分泌的假说 多肽是：1)受神经递质修饰调节 神经功能，通过改变大脑POMC的物质 体内的多肽，以及按物质(CRF、糖皮质激素、β- 内啡肽)，调节垂体POMC的分泌 多肽；2)在下丘脑和 下丘脑外脑；3)不协调；4)依赖 神经解剖关系；5)独立于细胞 POMC多肽的含量。 我们将使用体外模型来研究很难的分泌物。 在活体内研究。古典主义的监管效果 神经递质对分泌物的影响将在静态 分离的胎鼠下丘脑细胞系统的测定 (RIA)POMC多肽(ACTH、α-MSH、β-内啡肽)和 将结果与细胞和灌流系统的结果进行比较 外植体。神经递质的药理拮抗作用- 将对改变的分泌物进行评估。神经递质在脑损伤中的作用 POMC多肽分泌将在细胞中进一步评估 下丘脑外前脑和延髓。的效果 随后将研究其他监管候选人，并 在下丘脑和下丘脑外细胞中进行比较。 慢性接触特定物质对分泌物的影响 还将对POMC多肽的含量进行评估。分子 POMC多肽的形式将被表征和摩尔 分析关系以表明分泌调节是否 协调的或不协调的。 完成这个项目将有助于理解生理学 调节POMC多肽的分泌，可能有助于 了解大脑对合成和加工的调节 POMC多肽，并可能导致研究阐明其中枢神经系统 功能和模型表明监管的变化是否 POMC多肽代谢产生或加重中枢神经系统 精神障碍(精神分裂症、小儿麻痹症、癫痫发作、婴儿痉挛)。