DEVELOPMENT OF CNS ALPHA-2 ADRENERGIC RECEPTOR SUBTYPES

描述：（申请人摘要）拟议项目的目标是 了解调节alpha-2发育的因素 肾上腺素能受体（A2 AR）亚型及其在脑中的功能。 这 将通过定义大鼠中A2 AR的发展模式来完成 脑定量放射配体放射自显影使用非选择性和 亚型特异性配体和亚型特异性抗体，以及 原位杂交检测编码受体亚型的mRNA。 的 这些受体系统的功能发展将通过以下方式进行研究： 检查G蛋白和第二信使系统的耦合。 正常 使用去甲肾上腺素能神经元的特定损伤将破坏功能 以进一步了解调节A2 AR发展的因素。 有待检验的假设是：1）A2 AR亚型的发展， 这种发展的调节是区域和亚型特异性的，和2） A2 AR的正常发育，包括它们的功能，依赖于正常的 在发育的关键时期去甲肾上腺素能神经支配。

DESCRIPTION: (Applicant's abstract) The goal of the proposed project is to gain an understanding of the factors which regulate development of alpha-2 adrenergic receptor (A2AR) subtypes and their function in the brain. This will be accomplished by defining patterns of development of A2AR in rat brain by quantitative radioligand autoradiography using non-selective and subtype-specific ligands, and subtype-specific antibodies, as well as in situ hybridization to detect mRNAs encoding receptor subtypes. The functional development of these receptor systems will be studied by examining coupling to G-proteins and second messenger systems. Normal function will be disrupted using specific lesions of noradrenergic neurons to gain further insights into factors regulating A2AR development. Hypotheses to be tested are: 1) that development of A2AR subtypes and regulation of this development is region and subtype specific, and 2) that normal development of A2AR, including their function, is dependent on normal noradrenergic innervation during critical periods of development.