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RELATED MOLECULAR AND PHYSIOLOGICAL EVENTS IN VISION

视觉中的相关分子和生理事件

基本信息

批准号：
3255326
负责人：
SANFORD E OSTROY
金额：
$ 13.63万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-05-01 至 1992-02-29
项目状态：
已结题

项目摘要

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化学物质光感受器的反应和生理功能，目前的重点是脊椎动物光感受器的代谢。细胞的代谢反应直接提供ATP，特别是重要的是光感受器的运作的主要活动运输系统和磷酸化的某些组分如视紫红质和视紫红质的中间体，磷脂酰肌醇循环它们间接提供GTP，非常活跃的cGMP合成和G- proteins. 代谢反应也会影响烟酰胺辅酶（NAD+、NADP +/NADH、NADPH），在视紫红质循环中重要的化合物，还原视黄醇和氧化视黄醇。的一个区域调查涉及反应的识别，或调节脊椎动物代谢率的成分光感受器例如，我们的初步数据表明，磷酸果糖激酶是糖酵解中的一种酶，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，黑暗，各种程度的照明，和浓度的代谢底物（如葡萄糖）或效应物（如钙）。利用哺乳动物的视网膜，我们希望确定这些条件影响代谢率、高浓度的能源核苷酸和核苷酸辅酶，反过来，如何这些影响光感受器维持其离子的能力浓度，电生理反应，视紫红质循环和结构完整性。我们已经证明，在某些条件下发生的代谢率变化（例如因为漂白水平为10%）不足以维持ATP， GTP浓度。我们还观察到视紫红质在漂白水平高于4%时再生减少，在某些糖酵解抑制剂的存在下消除。一调查的第三个方面是，光感受器代谢伴随特定的内分泌（例如，糖尿病）或视网膜（例如，变性）疾病。信息哺乳动物在许多情况下的光感受器代谢可以提供定义临床问题的基础并接受治疗。我们最后一个调查领域是光感受器组件和反应之间的关系，光感受器的电生理特性。