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DUAL PATHWAYS REGULATING ACTH SECRETION

调节 ACTH 分泌的双重途径

基本信息

批准号：
3446216
负责人：
Louise M Bilezikjian
金额：
$ 5.61万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446216
关键词：
adrenocorticotropic hormone angiotensins catecholamines cyclic AMP gel electrophoresis hormone regulation /control mechanism lipid metabolism phospholipids radiotracer scintillation spectrometry tissue /cell culture vasopressins

项目摘要

This project is designed to provide an understanding of the basic cellular mechanisms regulating ACTH release. In both cultured rat anterior pituitary cells and in the ACTH secreting AtT20 cell line, the action of CRF has been proposed to be mediated by cyclic AMP. However, other secretagogues of ACTH such as angiotensin, vasopressin, the catecholamines and phorbol myristate acetate evoke ACTH secretory responses by activating postreceptor events that appear to be independent of cyclic AMP generation. These observations are consistent with the existence of more than one mechanism regulating this system. The AVP receptor in the anterior pituitary appears to be a V1-like receptor, activation of which, in other tissues, is associated with changes in phospholipid metabolism. Metabolities (i.e., 1,2-diacylglycerol) of this process, in turn, have been shown to activate a Ca2+/phospholipid-dependent protein kinase (C-kinase). The studies proposed in this grant will primarily deal with the mechanism of action of AVP and its interaction with CRF. These experiments will demonstrate the effect of AVP on both phospholipid turnover as well as C-kinase activation. If, in fact, CRF primarily utilizes a cAMP-dependent pathway, as previously shown, while the effects of AVP are mediated by C-kinase, the consequences of the activation of these pathways will be demonstrated by probing for endogenous phosphorylated substrates. This approach will provide a better understanding of how ACTH release is regulated by multiple hormonal influences.

这个项目的目的是提供一个基本的细胞的理解调节ACTH释放的机制。在两种培养的大鼠前额叶垂体细胞和分泌ACTH的AtT 20细胞系中，已提出慢性肾衰竭是由环磷酸腺苷介导的。但其他促ACTH分泌素，如血管紧张素、加压素、儿茶酚胺和佛波醇肉豆蔻酸酯通过激活似乎不依赖于环AMP的受体后事件一代这些观察结果与存在更多的一个机制来管理这个系统。精氨酸加压素受体垂体前叶似乎是V1样受体，其激活，在其他组织中，与磷脂代谢的变化有关。代谢（即，1，2-二酰基甘油），反过来，已经被显示激活Ca 2 +/磷脂依赖性蛋白激酶（C-激酶）。这项拨款建议进行的研究，主要是研究 AVP的作用及其与CRF的相互作用。这些实验将证明AVP对磷脂周转以及 C-激酶激活。事实上，如果CRF主要利用cAMP依赖性如前所述，AVP的作用是通过 C-激酶，这些途径激活的后果将是通过探测内源性磷酸化底物证实。这这种方法将更好地了解ACTH的释放是如何受多种激素影响。