MOLECULAR CHARACTERIZATION OF ANGIOTENSIN II RECEPTORS

血管紧张素II是一种来源于肾素-血管紧张素原的八肽 一种引起与监管有关的广泛影响的制度 血压与盐分和水分代谢有关。事实上，最多的 有效的人类高血压治疗剂通过阻断 血管紧张素的形成II。的广泛和长期目标 拟议的研究是血管紧张素II的分子特征。 感受器。此应用程序的特定目标是研究 血管紧张素II、1型受体分子的新形式 克隆自大鼠脑下垂体前叶。此克隆不同于 血管紧张素II，1型受体最近被描述为血管 平滑的肌肉和肾脏。脑下垂体形式的受体有一个 总体上，在核苷酸水平上与血管/肾脏的同源性为74% 受体；然而，它编码的蛋白质有95%的氨基酸同源性。 这两种受体形式的差异与 另一种RNA剪接表明，垂体和血管/肾 受体由不同的基因编码。配基结合 这两种受体的特征是相似的。他们的组织 在脑垂体和脑血管中的表达略有不同 平滑肌细胞显示出最高水平的同源受体。 最后，脑下垂体的信使核糖核酸水平受到雌激素的强烈调控。 该提案的具体目的是：1)比较配体结合 两种受体的特征；2)识别第二种受体 脑垂体型受体所利用的信使系统；3) 确定编码这两种基因的mRNAs的不同组织分布 受体的形式；4)检测雌激素对mRNA表达的影响 不同组织中两种形式的受体；5)克隆、测序和 确定该受体的脑垂体型编码基因；6) 分离、测序和鉴定人类形式的脑下垂体 受体；7)确定两种受体的细胞定位 使用原位杂交的m RNA，以及；8)产生单抗 从这两种受体衍生的多肽。这些研究 应该为人类的病因和治疗提供新的信息 高血压。

Angiotensin II is an octapeptide derived from the renin-angiotinsenogen system which evokes a broad spectrum of effects related to regulation of blood pressure and to salt and water metabolism. Indeed, the most effective therapeutic agent for human hypertension acts by blocking the formation of angiotensin II. The broad, long-term objective of the proposed studies is the molecular characterization of angiotensin II receptors. The specific objective of this application is the study of an apparently new form of the angiotensin II, type 1 receptor molecularly cloned from the rat anterior pituitary gland. This clone differs from the angiotensin II, type 1 receptor recently described for vascular smooth muscle and kidney. The pituitary form of the receptor has an overall 74% identity at the nucleotide level with the vascular/kidney receptor; however, it encodes a protein with a 95% amino acid identity. The differences in the two forms of receptors are not consistent with alternative RNA splicing suggesting that the pituitary and vascular/renal receptors are encoded by separate genes. The ligand binding characteristics of the two forms of receptors are similar. Their tissue mRNA expression differs somewhat in that the pituitary and vascular smooth muscle show the highest levels of their cognate receptors. Finally, pituitary levels of mRNA are strongly regulated by estrogens. The Specific Aims of the proposal are to: 1) compare the ligand-binding characteristics of the two forms of receptors; 2) identify the second messenger system utilized by the pituitary form of the receptor; 3) determine the differential tissue distribution of mRNAs encoding the two forms of receptors; 4) test the effects of estrogens on mRNA expression of the two forms of receptors in various tissues; 5) clone, sequence, and characterize the gene encoding the pituitary form of the receptor; 6) isolate, sequence, and characterize the human form of the pituitary receptor; 7) determine the cell localization of the two forms of receptor mRNA using in situ hybridization, and; 8) produce monoclonal antibodies to peptides derived from the two forms of receptors. These studies should provide new information about the etiology and treatment of human hypertension.