REGULATION OF SECRETION OF POMC PEPTIDES IN BRAIN

各种行为、生物化学和神经调节作用 在大脑中由促肾上腺皮质激素，α-MSH，β- 内啡肽及其加工过程中产生的相关肽 前体阿黑皮素原（POMC）， by neurons神经元. 尽管有各种体内研究， POMC相关肽的大脑水平的不同变量， 明确POMC的生理调节概念 脑中的肽仍有待确定。 了解 通过描绘电位调节脑POMC肽 生理调节剂，各种物质将被研究 对于改变POMC肽从脑的分泌的作用 细胞 我们将检验POMC的脑分泌 肽是：1）调节神经递质修饰 神经元功能，通过修饰脑POMC的物质 肽在体内，并通过物质（CRF，糖皮质激素，β- 内啡肽），调节垂体POMC的分泌 肽; 2）在下丘脑和 下丘脑外脑; 3）不协调; 4）依赖 神经解剖学关系; 5）独立于细胞 POMC肽的含量。 我们将使用体外模型来研究分泌， 在体内进行研究。 经典的调节效应 神经递质对分泌的影响将在静态 分离的胎鼠下丘脑细胞的测量系统 (RIA)POMC肽（ACTH、α-MSH、β-内啡肽）和 将结果与细胞灌流系统中的结果进行比较， 外植体 神经递质的药理学拮抗作用- 将评估改变的分泌。 神经递质对 POMC肽分泌将在来自以下的细胞中进一步评估： 下丘脑外前脑和延髓。 的影响 随后将研究其他监管候选人， 下丘脑和下丘脑外的细胞比较。 长期接触某些物质对分泌的影响 还将评估POMC肽的含量。 分子 POMC肽的形式将被表征， 分析关系以表明分泌调节是否 协调或不协调。 完成这个项目将有助于了解生理 调节POMC肽的分泌，可以帮助 了解大脑对合成和加工的调节 POMC肽，并可能导致研究阐明其中枢神经系统 功能和模型，表明是否改变监管 POMC肽代谢产生或加重CNS 疾病（精神分裂症、SIDS、癫痫发作、婴儿痉挛）。

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).