NICOTINIC RECEPTORS AUTONOMIC GANGLIA AND ADRENAL GLAND

烟碱受体自主神经节和肾上腺

• 批准号: 6841602
• 负责人: KENNETH J KELLAR
• 金额: $ 34.92万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6841602
• 关键词: adrenal glands; antireceptor antibody; autonomic ganglion; endocrine pharmacology; laboratory rat; neuropharmacology; nicotine; nicotinic receptors; receptor binding; receptor expression; voltage /patch clamp

DESCRIPTION(Adapted from applicant's abstract): The objectives of the studies described in this application are to compare the subunit composition, pharmacological profile and regulation of neuronal nicotinic receptors in rat autonomic ganglia and adrenal glad. In addition to their intrinsic physiological importance, these neuronal tissues are affected by nicotine and thus provide excellent model systems in which to explore the relationships between receptor subunit composition, pharmacology and regulation of nicotinic receptors by acute and chronic exposure to nicotine. Until recently it would have been difficult to develop a full understanding of the subunit composition, comparative pharmacology and regulation of native nicotinic receptor subtypes in mammalian neuronal tissues because of limitations in the methods and tools available to reliably measure and identify these receptor subtypes in native tissues. We believe these constraints can now be overcome. In the studies described here we will use the high affinity ligands [3H]epibatidine, [125I]epibatidine and [125I]A85380 to label these receptors in autonomic ganglia and adrenal gland and subunit-specific antibodies to determine the subunit composition of the receptors in each tissue. We will then examine the function of these receptor subtypes and determine how acute and chronic exposure to nicotine affects each. Thus, the specific aims of these studies are to: 1) compare the subunit composition of the receptors in these autonomic ganglia and adrenal gland; 2) compare the pharmacological characteristics of the different subtypes of these native receptors; 3) compare the pharmacological characteristics of the native receptors in these tissues with those in defined receptor subtypes stably expressed in mammalian cells; 4) examine the function and pharmacology of the nicotinic receptors in the rat adrenal gland in vivo; and 5) examine the regulation of the function and density of the nicotinic receptors in rat adrenal gland and ganglia after acute and chronic exposure to nicotine.

描述(改编自申请人的摘要)： 本申请中描述的研究的目标是比较 神经元亚单位组成、药理作用及其调控 大鼠自主神经节和肾上腺GREE的烟碱受体。除了……之外 它们内在的生理重要性，这些神经元组织会受到影响 因此提供了很好的模型系统来探索尼古丁 受体亚基组成、药理与调节的关系 由于急性和长期接触尼古丁，尼古丁受体的活性下降。直到 最近，我们很难完全理解 天然药物的亚基组成、比较药理学及调控 哺乳动物神经组织中烟碱受体亚型的研究 可用于可靠测量和识别的方法和工具的局限性 天然组织中的这些受体亚型。 我们相信，这些限制现在可以克服。在这里描述的研究中 我们将使用高亲和力配体[~3H]表巴替丁、[125I]表巴替丁和 [125I]A85380标记自主神经节和肾上腺中的这些受体 和亚基特异性抗体，以确定亚基组成 每个组织中的受体。然后我们将检查这些受体的功能 并确定急性和长期接触尼古丁对每个亚型的影响。 因此，这些研究的具体目的是：1)比较亚基 这些自主神经节和肾上腺的受体组成；2) 比较它们不同亚型的药理特性 天然受体；3)比较天然受体的药理特性 这些组织中的受体与那些确定的受体亚型的受体稳定 在哺乳动物细胞中表达；4)检测该蛋白的功能和药理 体内大鼠肾上腺中的尼古丁受体；以及5)检查 大鼠烟碱受体功能和密度的调节 急性和慢性尼古丁暴露后的肾上腺和神经节。