RAPID CELLULAR EFFECTS OF 1,25 DIHYDROXYVITAMIN D3

1,25 二羟基维生素 D3 的快速细胞作用

基本信息

批准号：
3238763
负责人：
DANIEL T. BARAN
金额：
$ 13.37万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-08-01 至 1990-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3238763
关键词：
1,25 dihydroxycholecalciferol acylation arachidonate calcium metabolism cell membrane cytoplasm epinephrine hormone regulation /control mechanism inositol laboratory rat liver cells membrane reconstitution /synthesis phosphatidylinositols phospholipase A2 phospholipids phosphorylases physical chemical interaction prostaglandins

项目摘要

Recent studies have documented that 1,25 dihydroxyvitamin D3 exerts cellular effects on a variety of tissues. Rapid actions of the vitamin D metabolite on the intestine and hepatocyte raise the possibility that the mechanism is independent of genome activation, perhaps attributable to a direct interaction with membranes. 1,25 dihydroxyvitamin D3 induces the deacylation of hepatocyte membrane phosphatidylinositol resulting in increased levels of glycerophosphorylinositol and presumably arachidonic acid within 5 minutes. In addition, 1,25 dihydroxyvitamin D3 rapidly increases hepatocyte cytosolic calcium, an effect which appears to be due to the mobilization of intracellular calcium stores and appears to be mediated by a deacylation product of phosphatidylinositol. These effects of 1,25 dihydroxyvitamin D3 on phosphatidylinositol and cytosolic calcium are blocked by inhibitors of phospholipase A activity. Comparable biochemical effects of similar magnitude mediate epinephrine's action on platelets. The proposed research will determine the relationship of these rapid, presumably membrane-mediated actions of 1,25 dihydroxyvitamin D3 to the effects of the metabolite on hepatocyte 25 hydroxyvitamin D synthesis. The effects of the metabolite on glycogen phosphorylase, an enzyme activated by increased cytosolic calcium, will also be investigated. Inhibitors of phospholipase A, the metabolically inactive 1 beta, 25 dihydroxyvitamin D3, and isolated hepatic membranes will be employed to further elucidate the nature of the membrane actions of 1,25 dihydroxyvitamin D3. The actions of the vitamin on Na+/H+ exchange as a modulator of phospholipase A activity will be investigated. The specificity of the vitamin's actions on inositol phospholipids will be examined as well as the relationship of increased phospholipid deacylation to hepatocyte prostaglandin production.

最近的研究证明 1,25 二羟基维生素 D3 对多种组织发挥细胞作用。快速行动肠道和肝细胞上的维生素 D 代谢升高该机制独立于基因组的可能性激活，可能归因于与膜。 1,25 二羟基维生素 D3 诱导脱酰化肝细胞膜磷脂酰肌醇增加甘油磷酸肌醇和大概花生四烯酸的水平 5 分钟内酸。此外，1,25二羟基维生素D3 迅速增加肝细胞胞质钙，这种作用似乎是由于细胞内钙的动员储存并似乎是由脱酰化产物介导的磷脂酰肌醇。 1,25 二羟基维生素 D3 的这些作用磷脂酰肌醇和胞质钙被阻断磷脂酶A活性抑制剂。可比生化类似程度的影响介导肾上腺素的作用血小板。拟议的研究将确定这种关系这些快速的、可能是膜介导的作用 1,25 二羟基维生素 D3 对代谢物的影响肝细胞25羟基维生素D的合成。的影响糖原磷酸化酶的代谢物，一种由细胞质钙增加，也将被研究。抑制剂磷脂酶 A，代谢不活跃的 1 beta，25 二羟基维生素 D3 和分离的肝膜将用于进一步阐明膜作用的性质 1,25 二羟基维生素 D3。维生素的作用 Na+/H+ 交换作为磷脂酶 A 活性的调节剂被调查。维生素作用的特异性将检查肌醇磷脂及其关系磷脂脱酰作用增加对肝细胞前列腺素的影响生产。