RELATED MOLECULAR AND PHYSIOLOGICAL EVENTS IN VISION

视觉中的相关分子和生理事件

• 批准号: 3255319
• 负责人: SANFORD E OSTROY
• 金额: $ 13.06万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-05-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3255319
• 关键词: 6 phosphofructokinase; Anura; Urodela; active transport; adenosine triphosphate; cellular respiration; cofactor; conformation; cyclic GMP; diabetic ophthalmopathy; electrophysiology; enzyme mechanism; fresh water environment; glycolysis; guanine nucleotides; laboratory mouse; light adaptations; membrane proteins; molecular biology; neurophysiology; phosphatidylinositols; phosphorylation; photochemistry; regeneration; retina degeneration; rhodopsin; spectrometry; vision; visual photoreceptor

The overall goal of the research program is to study the chemical reactions and physiological functions of the photoreceptor, with a present emphasis on the metabolism of vertebrate photoreceptors. The metabolic reactions of a cell directly provide ATP, especially important to photoreceptors for the operation of primary active transport systems and for the phosphorylation of certain components such as rhodopsin and intermediates of the phosphatidylinositol cycle. They indirectly provide GTP, required for the very active synthesis of cGMP and the control of G- proteins. Metabolic reactions also affect the concentration of nicotinamide coenzymes (NAD+,NADP+/NADH,NADPH), compounds that are important in the rhodopsin cycle for the reduction of retinal and the oxidation of retinol. One area of investigation involves identification of the reaction(s) or components that regulate metabolic rates in vertebrate photoreceptors. For example, our initial data suggest that phosphofructokinase, an enzyme within glycolysis, mediates respiratory responses to light. A second area of study is the metabolic effects of typical physiological condtions such as darkness, various levels of illunination, and concentrations of metabolic substrates (such as glucose) or effectors (such as calcium). Using mammalian retinas we wish to determine how these conditions affect metabolic rates, concentrations of high energy nucleotides and nucleotide coenzymes, and, in turn, how these affect the ability of photoreceptors to maintain their ion concentrations, electrophysiological responses, rhodopsin cycle and structural integrity. We have already shown that the metabolic rate changes that occur under certain conditions (such as bleaching levels of 10%) are inadequate to maintain ATP and GTP concentrations. We have also observed that rhodopsin regeneration is reduced at bleaching levels above 4% and eliminated in the presence of certain glycolytic inhibitors. A third area of investigation is whether abnormalities in photoreceptor metabolism accompany specific endocrine (e.g., diabetes) or retina (e.g., degenerative) disorders. Information on mammalian photoreceptor metabolism under many circumstances may provide a basis from which clinical problems can be defined and treated. Our final area of investigation is the relationship between photorecptor components and reactions, and the electrophysiological properties of the photorecptor.

研究计划的总体目标是研究这种化学物质。 光感受器的反应和生理功能，具有 目前重点关注脊椎动物光感受器的新陈代谢。 细胞的代谢反应直接提供三磷酸腺苷，尤其是 光感受器在初级活动中的重要作用 运输系统和某些特定蛋白的磷酸化 视紫红质等成分及其中间体 磷脂酰肌醇循环。它们间接提供GTP，需要 对于cGMP的非常活性的合成和对G- 蛋白质。新陈代谢反应也会影响体内 烟酰胺辅酶(NAD+、NADP+/NADH、NADPH)， 在视紫红质循环中对 视网膜缩小，视黄醇氧化。某一领域 调查涉及确定反应(S)或 调节脊椎动物代谢率的成分 光感受器。例如，我们的初始数据表明 磷酸果糖激酶，糖酵解中的一种酶，调节 对光的呼吸反应。第二个研究领域是 典型生理条件的代谢效应，如 黑暗，不同程度的幻觉，以及 代谢底物(如葡萄糖)或效应物(如 钙)。利用哺乳动物的视网膜，我们希望确定如何 这些情况会影响代谢率，高浓度的 能量核苷酸和核苷酸辅酶，进而，如何 这些都会影响光感受器维持离子的能力。 浓度、电生理反应、视紫红质循环 和结构的完整性。我们已经证明了 在特定条件下(如 因为10%的漂白水平)不足以维持ATP和 GTP浓度。我们还观察到视紫红质 当漂白程度超过4%时，再生减少 在某些糖酵解抑制剂存在的情况下消除。一个 调查的第三个领域是异常情况是否 光感受器代谢伴随着特定的内分泌(例如， 糖尿病)或视网膜(例如，退行性)疾病。有关的信息 哺乳动物在多种情况下的光感受器代谢 可以提供一个定义临床问题的基础 并接受治疗。我们调查的最后一个领域是 光接收器组件和反应之间的关系，以及 光接收器的电生理特性。