BETA1 AND BETA3 ADRENORECEPTORS

β3肾上腺素能受体已被认为是一种治疗 肥胖症和成人糖尿病的治疗目标，但非常 对其生化和药理特性知之甚少。 这些受体。药理和分子数据表明 脂肪组织同时含有Beta1和Beta3受体，但目前尚不清楚 为什么脂肪细胞会产生这两种受体亚型。我们的初步数据， 然而，这表明Beta1和Beta3受体具有不同的信号- 转导特性，受激动剂的差异调节 曝光。我们建议进一步描述这些差异，并 研究这些差异的分子基础。 我们发现人类Beta3受体基因含有一个内含子。 和第二个编码蛋白质的外显子。所有以前与重组的工作 人类Beta3受体是在一种缺少该序列的蛋白质上进行的 来自第二个外显子，因此是不完整的。此外，初步的 数据表明，新发现的外显子可能起到重要作用 人类受体的药理和调节特性。 我们还发现，大鼠的Beta3受体基因也包含 多个外显子和内含子。大鼠第一个内含子的序列 基因提示它可能在脂肪特异性表达中发挥作用。我们的 具体目标是： 1.首次鉴定其药理性质 重组全长人β3受体的表达。为了进一步 描述Beta1和Beta3的差异信号特性 感受器。 2.研究Beta1和Beta3的差异调控 通过激动剂暴露受体并检查其分子基础。 3.评估差动信令特性的影响 β1和β3受体对脂肪细胞生理反应的影响。 4.确定赋予脂肪组织特异性的遗传因素 大鼠β3受体的表达，最初的焦点是 第一内含子的潜在作用。以确定人类Beta3是否 受体基因含有相似的元件。

The beta3 adrenergic receptor has been proposed to be a therapeutic target for the treatment of obesity and adult-onset diabetes, yet very little is known about the biochemical and pharmacological properties of these receptors. Pharmacological and molecular data indicate that adipose tissues contain both beta1 and beta3 receptors, yet it is unclear why fat cells make both receptor subtypes. Our preliminary data, however, indicate that beta1 and beta3 receptors have distinct signal- transducing properties and are differentially regulated by agonist exposure. We propose to further characterize these differences and examine the molecular bases of those differences. We have discovered that he human beta3 receptor gene contains an intron and a second protein-coding exon. All previous work with the recombinant human beta3 receptor was conducted on a protein that lacked the sequence from the second exon, and thus was incomplete. Furthermore, preliminary data indicates that the newly-discovered exon may play an important role in the pharmacological and regulatory properties of the human receptor. We have also discovered that the rat beta3 receptor gene also contains multiple exons and introns. The sequence of the first intron of the rat gene suggest that it may play a role in fat-specific expression. Our specific aims are: 1. To characterize, for the first time, the pharmacological properties of the recombinant full-length human beta3 receptor. To further characterize the differential signalling properties of beta1 and beta 3 receptors. 2. To characterize the differential regulation of beta1 and beta3 receptors by agonist exposure and to examine the molecular basis. 3. To evaluate the impact of the differential signalling properties of beta1 and beta3 receptors on physiological responses in adipocytes. 4. To determine the genetic elements that confer adipose tissue-specific expression of the rat beta3 receptor, with a initial focus on the potential role of the first intron. To determine whether the human beta3 receptor gene contains similar elements.