A-ADRENERGIC RECEPTOR BINDING AND FUNCTION IN THE BRAIN

我们建议检查的绑定和功能属性 大鼠脑内α-肾上腺素能受体亚型的定位 特定的细胞类型和神经束，受体密度的调节 以及通过传入输入的改变和交互的反应 在大脑中有这些受体的各种精神活性药物。字母1-和 将使用该拮抗剂直接标记α2-肾上腺素能受体 放射性配体125I-BE2254和~3H-Rauwolscine。泛函的度量 对受体刺激的反应将包括去甲肾上腺素诱导 ~3H-肌醇代谢增加和可乐定引起的减少 α1和α2肾上腺素能对脑片环磷酸腺苷水平的影响 分别为受体。减少~3H-5-羟色胺的释放 还将在大鼠身上检测α2-肾上腺素能受体刺激 大脑皮层。两种拮抗剂的效力之间的相关性 放射性配基结合位点的竞争与受体介导的抑制 回应将提供放射性配基正在标记的证据 合适的受体位置。激动剂效价的比较 结合受体和激活功能反应将估计 受体占有率与组织反应之间的关系。这个 备用受体的存在将通过减少受体来检查 苯氧基苯甲胺的浓度和条件下的响应性检测 受体密度降低。受体亚型定位于 特定的细胞群和神经束将通过以下方式完成 化学损伤后和散装分离后受体密度的检测 细胞群。受体密度和反应性的调节 去甲肾上腺素能输入的改变，以及慢性激动剂或拮抗剂 治疗，将为控制适应性的机制提供证据 这些受体的反应性。慢性阻塞性肺疾病后的疗效观察 精神活性药物的治疗将提供哪些药物的证据 与这些受体有显著的相互作用。这些实验将 增加我们对属性、本地化和监管的知识 大鼠脑内α-肾上腺素能受体亚型。这将在 了解去甲肾上腺素在大脑中的作用，以及在 评估一些药物对中枢神经系统的影响 与阿尔法肾上腺素能受体相互作用，目前医学中 用法。

We propose to examine the binding and functional properties of Alpha-adrenergic receptor subtypes in rat brain, their localization to specific cell types and nerve tracts, the regulation of receptor density and responsiveness by changes in afferent input, and the interaction of various psychoactive drugs with these receptors in the brain. Alpha1- and Alpha2-adrenergic receptors will be directly labelled using the antagonist radioligands 125I-BE2254 and 3H-rauwolscine. Measurement of functional responses to receptor stimulation will include norepinephrine-induced increases in 3H-inositol metabolism and clonidine-induced decreases in cyclic AMP levels in brain slices by Alpha1- and Alpha2-adrenergic receptors respectively. Decreases in 3H-5-hydroxytryptamine release by Alpha2-adrenergic receptor stimulation will also be examined in rat cerebral cortex. Correlation between the potencies of antagonists in competing for radioligand binding sites and inhibiting receptor-mediated responses will provide evidence that the radioligands are labelling the appropriate receptor sites. Comparison of the potencies of agonists in binding to the receptors and activating functional responses will estimate the relationship between receptor occupancy and tissue response. The existence of spare receptors will be examined by decreasing receptor density with phenoxybenzamine and examining responsiveness under conditions of decreased receptor density. Localization of receptor subtypes to specific cell populations and nerve tracts will be accomplished by examination of receptor density after chemical lesions and in bulk isolated cell populations. The regulation of receptor density and responsiveness by alterations in the noradrenergic input, and chronic agonist or antagonist treatment, will provide evidence on mechanisms controlling the adaptive responsiveness of these receptors. Effects observed after chronic treatment with psychoactive drugs will provide evidence as to which drugs have significant interactions with these receptors. These experiments will increase our knowledge of the properties, localization and regulation of Alpha-adrenergic receptor subtypes in rat brain. This will be useful in understanding the actions of norepinephrine in the brain, as well as in evaluating the central nervous system effects of a number of drugs that interact with Alpha-adrenergic receptors and that are in current medical usage.