THE CONTROL OF TISSUE-SENSITIVITY TO AUTONOMIC AGENTS

组织对自主代理的敏感性的控制

• 批准号: 3255316
• 负责人: LASZLO Z. BITO
• 金额: $ 20.07万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3255316
• 关键词: autonomic agents; cholinergic agents; drug hypersensitivity; drug metabolism; drug tolerance; eye coordination disorder; eye pharmacology; glaucoma; meiosis; ocular hypotensive; pupillography; ultrasonography; visual photosensitivity

The long-term objective of this project is to test the hypotheses, which were proposed by us in previous years and are now gaining acceptance, that the sensitivity of target organs is a dynamic phenomenon controlled by inherent feedback mechanisms; that experimental manipulation of this sensitivity provides a new avenue for studying individual components of complex systems like the eye, in which several target organs have the same pharmacological characteristics; that such alterations in target organ sensitivity may affect the efficacy of drugs; and that the cause of some disorders involves the failure of such control mechanisms which, once identified, can be corrected by pharmacological means. Our specific aims for the next five-years will be to elucidate the nature and specificity of pharmacologically- (DFP, pilocarpine, oxotremorine) and physiologically-induced (stimulus deprivation or overstimulation) sensitivity changes, using intraocular muscles as primary model systems. We will develop techniques to induce subsensitivity in the iris sphincter without affecting the sensitivity of the ciliary muscles, to induce specific subsensitivity in each subcomponent of the muscarinic system, and will use the techniques of selective sensitivity alterations as one means of analyzing the complexity of the muscarinic system. We will further test the hypothesis that such changes in sensitivity are associated with changes in the concentration of (different subpopulations of) muscarinic receptors. We will also study the effects of altered iris sphincter and ciliary muscle sensitivity on the normal functions of these organs using pupillographic and ultrasonic techniques, respectively. Elucidation of the mechanism of the control of target organ sensitivity is of great general significance with regard to virtually all areas of biomedical science and especially with regard to the eye, where autonomic agents are used chronically for the treatment of glaucoma and accomodative esotropia. Experiments aimed at identifying the endogenous factors responsible for episodes of sustained miosis in cholinergically subsensitive rhesus eyes will also be undertaken. Such studies may explain the cause of sustained miosis in the eyes of cholinesterase inhibitor-treated patients, which should be subsensitive to ACh, and reveal some, as yet unknown, basic aspects of cholinergic mechanisms.

该项目的长期目标是检验假设， 我们在前几年提出的，现在正在获得接受，即 靶器官的敏感性是一个动态现象，受控于 固有的反馈机制；对此的实验操纵 敏感性为研究单个成分提供了新途径 像眼睛这样的复杂系统，其中几个目标器官具有相同的功能 药理特性；靶器官的这种改变 敏感性可能会影响药物的疗效；以及某些原因 疾病涉及这种控制机制的失败，一旦 确定后，可以通过药理学手段进行纠正。 我们的具体目标 未来五年的目标是阐明 药理学-（DFP、毛果芸香碱、氧化震颤素）和 生理引起的（刺激剥夺或过度刺激） 使用眼内肌作为主要模型系统，敏感性发生变化。 我们将开发诱导虹膜括约肌不敏感的技术 不影响睫状肌的敏感性，诱导 毒蕈碱系统每个子成分的特定亚敏感性，以及 将使用选择性敏感性改变技术作为一种手段 分析毒蕈碱系统的复杂性。 我们将进一步测试 假设这种敏感性的变化与变化有关 毒蕈碱（不同亚群）的浓度 受体。 我们还将研究虹膜括约肌改变的影响 睫状肌敏感性对这些器官正常功能的影响 分别是瞳孔描记术和超声技术。 阐明 靶器官敏感性的控制机制具有很大的普遍性 对生物医学科学的几乎所有领域都具有重要意义 尤其是在使用自主神经剂的眼睛方面 长期用于治疗青光眼和调节性内斜视。 旨在确定造成这种现象的内源性因素的实验 胆碱能不敏感的恒河猴眼睛持续性瞳孔缩小发作 也将进行。 此类研究或许可以解释持续存在的原因 接受胆碱酯酶抑制剂治疗的患者眼睛出现瞳孔缩小， 应该对乙酰胆碱敏感，并揭示一些目前未知的基本信息 胆碱能机制的各个方面。