NICOTINIC RECEPTORS AUTONOMIC GANGLIA AND ADRENAL GLAND

描述（改编自申请人摘要）： 本申请中描述的研究的目的是比较 神经元亚单位组成、药理学特征和调节 大鼠自主神经节和肾上腺皮质的烟碱受体。除了 它们内在的生理重要性，这些神经元组织受到影响， 尼古丁，从而提供了很好的模型系统，在其中探索 受体亚单位组成、药理学和调节之间的关系 尼古丁受体的变化。直到 最近，很难全面了解 亚基组成、比较药理学和天然调节 哺乳动物神经元组织中的烟碱受体亚型， 可用于可靠测量和识别的方法和工具的局限性 这些受体亚型在天然组织中。 我们认为，这些制约因素现在可以克服。在这里描述的研究中， 我们将使用高亲和力配体[3 H]地棘蛙素、[125 I]地棘蛙素和 [125 I]A85380标记植物神经节和肾上腺中的这些受体 和亚单位特异性抗体，以确定亚单位的组成， 每个组织中的受体然后我们将研究这些受体的功能 亚型，并确定如何急性和慢性暴露于尼古丁影响每一个。 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中受体的组成; 2） 比较这些不同亚型的药理学特征， 天然受体; 3）比较天然受体的药理学特征， 这些组织中的受体与确定的受体亚型中的受体稳定 在哺乳动物细胞中表达; 4）检查 体内大鼠肾上腺中的烟碱受体;和5）检查 大鼠烟碱受体功能和密度的调节 急性和慢性暴露于尼古丁后的肾上腺和神经节。

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.