ONTOGENY OF BETA-ENDORPHIN IN THE MEDULLA OBLONGATA

有证据表明，婴儿猝死综合症是一种 中枢性呼吸中枢功能障碍的结果 神经系统。也有证据表明，外生性 阿片肽的给药可对血管产生降压作用 延髓呼吸中枢。因为延髓是 几组不同的神经元的位置，它们合成了 阿片前体前阿片黑素皮质素、前脑啡肽和前阿片皮质素 强啡肽，有可能存在这些内源性阿片类药物 肽系统可能调节延髓呼吸中枢。 这一领域的研究将得到动物模型研究的帮助 系统。 该提案侧重于支持阿片黑素皮质素的系统。 大鼠个体发育过程中的延髓。的目标 这些项目是为了确定是否有发展中的 前阿片肽蛋白水解度的变化- 黑素皮质素与β-内啡肽的N-乙酰化程度 在胎儿和新生儿发育后期。 该项目将分两个阶段进行。第一个系列 实验将涉及对以下形式的稳态分析 延髓中与阿片黑素皮质素原相关的终末产物。组织 在胎儿第16天、第18天和新生儿第1、7、14和21天采集 将通过凝胶过滤进行分离，并通过 一系列针对β-内啡肽、α-内啡肽的放射免疫测定 MSH和ACTH(1-39)。β-N-乙酰化度 内啡肽和α-MSH将通过离子交换测定 柱层析法和反相高效液相色谱法。 第二个系列的实验将尝试研究PRO- 胎儿延髓神经元中阿片黑素皮质素的生物合成途径 在文化上。分散的神经元将受到氚的冲击 酪氨酸和新合成的多肽将通过 免疫亲和层析和SDS-PAGE分析。 这些项目将提供对发展的见解 阿片黑素皮质素原系统在延髓的出现 长方形。这些信息将对设计有用 测试内源性神经递质潜在参与的实验 β-内啡在延髓呼吸抑制中的作用 很复杂。

There is evidence that Sudden Infant Death Syndrome occurs as a result of a dysfunction of the respiratory centers in the central nervous system. There is also evidence that exogenous administration of opioid peptides can exert depressor action on the medullary respiratory centers. Since the medulla oblongata is the site of several distinct sets of neurons which synthesize the opioid precursors pro-opio-melanocortin, pro-enkephalin and pro- dynorphin, the possibility exists that these endogenous opioid peptide systems may modulate the medullary respiratory centers. Research in this area would be aided by studies on animal model systems. This proposal focuses on the pro-opiomelanocortin system in the medulla oblongata of the rat during ontogeny. The objectives of these projects are to determine whether there are developmental changes in the degree of proteolytic processing of pro-opio- melanocortin and the degree of N-acetylation of beta-endorphin during late fetal and neonatal development. The project will be approached in two phases. The first series of experiments will involve a steady state analysis of the forms of pro-opiomelanocortin-related end products in the medulla. Tissue collected at fetal day 16, day 18 and neonatal day 1, 7, 14, and 21 will be separately fractionated by gel filtration and analyzed by series of radioimmunoassays specific for beta-endorphin, alpha- MSH and ACTH(1-39). The degree of N-acetylation of beta- endorphin and alpha-MSH will be determined by ion exchange chromatography and reverse phase HPLC, respectively. The second series of experiments will attempt to study the pro- opiomelanocortin biosynthetic pathway in medullary fetal neurons in culture. Dispersed neurons will be pulsed with tritiated tyrosine and the newly synthesized peptides will be isolated by immunoaffinity chromatography and analyzed by SDS PAGE. These projects will provide insights into the developmental appearance of the pro-opiomelanocortin system in the medulla oblongata. This information will be useful for designing experiments to test the potential involvement of endogenous beta-endorphin in the depression of the medullary respiratory complex.