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α-2发育的因素 肾上腺素能受体(A2AR)亚型及其在脑中的功能。这 将通过确定A2AR在大鼠体内的发育模式来实现 应用非选择性放射自显影和放射自显影技术对脑进行定量研究 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mRNAs。这个 这些受体系统的功能发展将通过以下方式进行研究 检查与G蛋白和第二信使系统的偶联。正常 去甲肾上腺素能神经元的特定损伤将扰乱功能 以进一步了解调控A2AR发展的因素。 需要检验的假设是：1)A2AR亚型的发育和 对这一发展的调控是特定于地区和亚型的，以及2) A2AR的正常发育，包括其功能，依赖于正常 发育关键期的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.