LIPID - & PROTEIN PO4 TURNOVER IN IRIS OF THE EYE

脂质-

• 批准号: 3258698
• 负责人: ATA A ABDEL-LATIF
• 金额: $ 11.28万
• 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/3258698
• 关键词: alpha adrenergic agent; alpha antiadrenergic agent; drug metabolism; eye pharmacology; gel electrophoresis; inositol phosphates; intraocular pressure; iris; 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.

在虹膜肌肉中，眼睛的神经递质，如 乙酰胆碱和去甲肾上腺素与毒碱-胆碱能和 α1-肾上腺素能受体分别引起钙离子的动员， 这会导致细胞内钙离子的增加，从而导致 肌肉收缩。此外，神经递质-受体的相互作用 导致选择性地刺激酸性物质的周转 聚磷脂酰肌醇(PolyPI)中的磷脂 二磷肌醇(DPI)和三磷酸肌醇(TPI)。从我们的早期开始 神经递质诱导的大鼠脑内TPI损伤的特征 几位研究人员在不同的研究中观察到了这种现象 组织和现在被认为是激活中的初始反应 动员钙离子受体的关键是TPI分解成甘油二酯 (DG)和三磷酸肌醇(InP3)。潜在的分子机制 增强的TPI分解及其生理后果仍然是 不清楚。拟议的研究计划的目标是抛出更多 光，通过生物化学-药理学研究，对分子 机制(S)背后的相互关系 神经递质诱导的TPI分解、钙离子动员、DG诱导 蛋白激酶C激活与肌肉收缩和乳酸形成 兔子和牛的虹膜。 希望拟议的研究计划的结果将 扩大我们对生理作用和相对位置的理解 在连接的生化事件序列中的Ca~(2+)和聚PI 受体的激活对平滑肌的反应。此外，因为 磷脂酰肌醇周转是一种普遍的生化事件，我们的发现， 一如既往，无疑会适用于各种纸巾。最后， 我们建议的研究可望为下列事项提供更多资料： (A)提供关于以下机构的机制和职能的相关资料 眼部平滑肌肉中的M受体和α1肾上腺素能受体。 (B)磷脂和磷蛋白参与的性质 神经递质诱导的膜通透性和光照 磷酸盐重排在膜通透性调节中的作用 受体激活。(C)药理作用机制 眼睛。(D)房水形成机制，涉及 调节眼压。(E)对 虹膜平滑肌肉的生物化学、药理学和生理学。