LIPID - & PROTEIN PO4 TURNOVER IN IRIS OF THE EYE

脂质-

• 批准号: 3258697
• 负责人: ATA A ABDEL-LATIF
• 金额: $ 10.98万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-30 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3258697
• 关键词: alpha adrenergic agent; alpha antiadrenergic agent; drug metabolism; eye pharmacology; gel electrophoresis; inositol phosphates; intraocular pressure; lactates; membrane lipids; membrane permeability; muscle contraction; neurotransmitters; phosphates; phosphatidylinositols; phospholipids; phosphorylation; protein kinase C; radioassay; sarcoplasmic reticulum; smooth muscle; synapses

In the iris smooth muscle of the eye neurotransmitters such as acetylcholine and norepinephrine interact with muscarinic-cholinergic and Alpha 1-adrenergic receptors, respectively, to cause mobilizaiton of Ca2+, and this results in an increase in intracellular Ca2+ and consequently in muscle contraction. In addition, the neurotransmitter-receptor interaction results in a selective stimulation of the turnover of the acidic phospho-lipids which incude the polyphosphoinositides (poly PI) dicphosphoinositide (DPI) and triphosphoinositide (TPI). Since our early characterization of the neurotransmitter-induced breakdown of TPI in the iris several investigators have observed this phenomenon in a variety of tissues and it is believed now that the initial reaction in the activation of Ca2+ mobilizing receptors is the breakdown of TPI into diacylglycerol (DG) and inositol triphosphate (InP3). The underlying molecular mechanism of the enhanced TPI breakdown and its physiological consequences are still unclear. The goals of the proposed research program are to throw more light, through biochemical-pharmacological studies, on the molecular mechanism(s) underlying the interrelationships between neurotransmitter-induced TPI breakdown, Ca2+ mobilization, DG-induced protein kinase C activation and muscle contraction and lactate formation in rabbit and bovine irides. It is hoped that the findings from the proposed research program will extent our understanding of the physiological role and relative positions of Ca2+ and poly PI in the sequence of biochemical events that link receptor activation to smooth muscle response. Furthermore, because the phosphoinositide turnover is a universal biochemical event, our findings, as in the past, will undoubtedly apply to a variety of tissues. Finally, our proposed studies will, hopefully, throw more light on the following: (a) Yield relevant information with regard to the mechanism and function of muscarinic and Alpha 1-adrenergic receptors in smooth muscles of the eye. (b) Nature of the involvement of phospholipids and phosphoproteins in neurotransmitter-induced membrane permeability, and illumination of the phosphate rearrangement in regulation of membrane permeability during receptor activation. (c) Mechanism of action of pharmacological agents in the eye. (d) Mechanism of aqueous humor formation, which is involved in regulating intraocular pressure. (e) Mechanistic insights into the biochemistry, pharmacology, and physiology of the iris smooth muscle.

在眼睛的虹膜平滑肌中， 乙酰胆碱和去甲肾上腺素与毒蕈碱-胆碱能相互作用， α 1-肾上腺素能受体，分别引起Ca 2+的动员， 这导致细胞内Ca 2+增加， 肌肉收缩。 此外，神经递质-受体相互作用 导致选择性刺激酸性蛋白质的周转， 磷脂，包括聚磷酸肌醇（聚PI） 二磷酸肌醇（DPI）和三磷酸肌醇（TPI）。 自从我们的早期 神经递质诱导的TPI降解的表征 一些研究人员已经在各种各样的虹膜中观察到这种现象， 组织，现在人们相信激活的最初反应 Ca 2+动员受体的最大作用是TPI分解为甘油二酯 (DG)和肌醇三磷酸（InP 3）。 的分子机制 增强的TPI分解及其生理后果仍然是 不清楚 这项研究计划的目标是 光，通过生物化学-药理学研究，对分子 相互关系的内在机制 神经递质诱导的TPI分解，Ca 2+动员，DG诱导的 蛋白激酶C激活和肌肉收缩及乳酸形成 兔子和牛的虹膜。 希望拟议的研究计划的结果将 扩展我们对生理作用和相对位置的理解 Ca 2+和多聚PI在生化事件的序列中， 受体激活对平滑肌的反应。 此外，由于 磷脂酰肌醇转换是一个普遍的生物化学事件，我们的发现， 和过去一样，毫无疑问地将适用于各种组织。 最后， 我们建议进行的研究，希望能进一步阐明以下几点： (a)提供有关的机制和功能的信息， 眼睛平滑肌中的毒蕈碱和α 1-肾上腺素能受体。 (b)磷脂和磷蛋白参与的性质 神经递质诱导的膜渗透性，和照明的 磷酸重排在调节膜通透性过程中的作用 受体激活 (c)药物的作用机制 the eye. (d)水状体形成的机制，这是参与 调节眼内压。 (e)机械的见解， 虹膜平滑肌的生物化学、药理学和生理学。