STRUCTURE AND FUNCTION OF THE LYMPHOCYTE ACTH RECEPTOR

近年来，有人提出， 神经系统和免疫系统相互影响 可能是两者共同的配体和受体的结果 系统. 支持这一假设的证据来自 研究发现，淋巴细胞有能力产生许多 神经内分泌激素，包括促肾上腺皮质激素和内啡肽; 然而，直接的生化证据表明， 神经和免疫系统细胞上的受体缺乏。 因此，本提案的目的是表明， 一种特殊的受体淋巴细胞ACTH受体 就其结构和配体结合能力而言， 与肾上腺的对应物相比 在我们的实验室，肾上腺 促肾上腺皮质激素受体先前已被分离和表征 就其亚单位结构和结合ACTH的能力而言， 使用对受体有特异性的抗体 类似的研究还有 建议使用免疫亲和法测定淋巴细胞ACTH受体 色谱分离受体和随后的分析 聚丙烯酰胺凝胶的结构。 通过比较 肾上腺促肾上腺皮质激素受体的分子特征 从淋巴细胞受体获得的那些， 以确定这两种受体是否相似。 而肾上腺ACTH受体的功能是增加 肾上腺细胞的类固醇生成，淋巴细胞的功能 ACTH受体未知。 我们建议调查 淋巴细胞ACTH受体在分子水平上的功能 通过跟踪刺激后受体的调节， 淋巴细胞促肾上腺皮质激素，有丝分裂原，抗原，或选择 淋巴因子 刺激后，表面的表达 将使用免疫荧光技术跟踪受体 和随后的流式细胞术分析。 研究还将 研究ACTH结合对环核苷酸的影响， 水平和蛋白磷酸化。 ACTH 受体功能将通过比较生物学 抗受体抗体处理的淋巴细胞反应 与ACTH处理的细胞相比。 因此，本报告的总体目标 建议是比较淋巴细胞的分子结构 与其肾上腺对应物，并探讨其功能 在分子水平上对淋巴细胞促肾上腺皮质激素受体的影响

In recent years, it has been suggested that the ability of the nervous and immune systems to influence each other's function may be the result of ligands and receptors common to both systems. Evidence to support this hypothesis comes from the findings that lymphocytes have the ability to produce many of the neuroendocrine hormones including ACTH and the endorphins; however, direct biochemical evidence for the presence of common receptors on cells of the nervous and immune systems is lacking. Thus, the purpose of this proposal is to demonstrate that one particular receptor, the lymphocyte ACTH receptor, is identical with respect to its structure and ligand binding ability when compared to its adrenal counterpart. In our laboratory, adrenal ACTH receptors have been previously isolated and characterized with respect to their subunit structure and ability to bind ACTH using an antibody specific for the receptor. Similar studies are proposed for the lymphocyte ACTH receptor using immunoaffinity chromatography to isolate the receptors and subsequent analysis of the structure on polyacrylamide gels. By comparing the molecular characteristics of the adrenal ACTH receptor with those obtained from the lymphocyte receptor, it will be possible to determine if the two receptors are similar. While the adrenal ACTH receptor functions to increase steroidogenesis in adrenal cells, the function of the lymphocyte ACTH receptor is unknown. We propose to investigate the function of the lymphocyte ACTH receptor at a molecular level by following the modulation of receptors after stimulation of lymphocytes with ACTH, mitogens, antigen, or selected lymphokines. After stimulation, the expression of surface receptors will be followed using immunofluorescent techniques and subsequent flow cytometric analysis. Studies will also investigate the effects of ACTH binding on cyclic nucleotide levels and protein phosphorylation in lymphocytes. ACTH receptor function will be addressed by comparing biological responses of lymphocytes treated with anti-receptor antibody versus ACTH-treated cells. Thus, the overall objective of this proposal is to compare the molecular structure of the lymphocyte with that of its adrenal counterpart, and to explore the function of the lymphocyte ACTH receptor at a molecular level.