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1,25-DIHYDROXYVITAMIN D FUNCTION AND RECEPTOR OCCUPANCY

1,25-二羟基维生素 D 功能和受体占用

基本信息

批准号：
3152360
负责人：
MARIAN R WALTERS
金额：
$ 6.91万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1988-06-30
项目状态：
已结题

项目摘要

These studies will be directed toward (a) extending studies of occupied 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptor function to the rat, a major mammalian model for endocrine research, and (b) testing the hypothesis that the unexpectedly widespread tissue distribution of 1,25(OH)2D3 receptors reflects a heretofore unrecognized role for the vitamin D endocrine system in regulating intracellular calcium functions. The approach to this series of studies will be to use a particularly sensitive sucrose gradient receptor detection technique to seek 1,25(OH)2D3 receptors in a series of tissues where calcium is known to have a specialized role(s). Then the functionality of these receptors will be assessed by determining whether the receptors are occupied under physiological conditions and examining the tissues for a specific endpoint of 1,25(OH)2D3 action - the vitamin D induced calcium binding protein (CaBP). In order to analyze the occupied receptor sites we will develop a modified version of the exchange assay recently reported for the measurement of occupied 1,25(OH)2D3 receptors in the chick intestinal mucosa. The exchange assay for quantitation of occupied 1,25(OH)2D3 receptors in the rat will also be applied in studies to establish the dynamics of receptor occupancy and total receptor levels under a variety of physiological states in the rat and to compare their patterns to those previously described in the chick. These interrelated studies of 1,25(OH)2D3 receptor function will add much to our understanding of the vitamin D endocrine system and will provide a basis for future assessments of 1,25(OH)2D3 function in both normal and diseased individuals.

这些研究将针对（a）扩大研究占领 1，25-二羟维生素D3（1，25（OH）2D 3）受体对大鼠的功能，用于内分泌研究的主要哺乳动物模型，和（B）测试这一假说认为， 1，25（OH）2D 3受体反映了迄今为止未被认识的作用，维生素D对内分泌系统细胞内钙离子的调节作用。这一系列研究的方法将是使用一个特别的灵敏的蔗糖梯度受体检测技术寻找1，25（OH）2D 3 受体在一系列组织中，钙是已知有一个专门角色。那么这些受体的功能通过确定受体是否被占据来评估生理条件和检查组织的特定终点 1，25（OH）2D 3作用-维生素D诱导的钙结合蛋白（CaBP）。为了分析被占据的受体位点，我们将开发一个最近报道的交换试验的修改版本鸡肠道1，25（OH）_2D_3受体的测定粘膜用于定量占据的1，25（OH）2D 3的交换测定大鼠中的受体也将被应用于研究，以建立在各种条件下，受体占有率和总受体水平的动态大鼠的生理状态，并将其模式与之前在小鸡中描述过。这些相互关联的研究 1，25（OH）2D 3受体的功能将大大增加我们对维生素D内分泌系统，并将为未来的评估提供基础 1，25（OH）2D 3在正常和患病个体中均发挥作用。