CA2+ TRANSPORT BY INTESTINAL CELL MEMBRANE

肠细胞膜的 CA2 运输

• 批准号: 3447326
• 负责人: JULIAN R WALTERS
• 金额: $ 5.25万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447326
• 关键词: Golgi apparatus; basolateral membrane; cell membrane; endoplasmic reticulum; epithelium; gastrointestinal absorption /transport; ion transport; membrane permeability; mitochondria; osteomalacia; osteoporosis; vitamin D

The aim of this research is to delineate, in different intestinal epithelial cell types, the various subcellular membrane-related mechanisms which transport calcium. These membrane systems may be important in the physiological regulation of cytoplasmic free calcium as well as in transcellular calcium absorption. Membrane calcium-pumps can act by (i) extrusion of calcium from the cell across the baso-lateral membrane, and (ii) by sequestration of calcium within intracellular storage sites, which, in other tissues, occur in the endoplasmic reticulum, mitochondria and the Golgi apparatus. Evidence suggests such stores are involved in the distal small intestine in hormonal control of water and electrolyte secretion and absorption and thus are important in the pathogenesis and treatment of diarrheal diseases. In the proximal small intestine, calcium-pumps are involved in calcium transport across the epithelial cell during vitamin D-dependent active calcium absorption and so may be relevant in osteomalacia and senile osteoporosis. It is planned to investigate the differences in the subcellular membrane calcium-transport mechanisms in the proximal:distal intestinal gradient of function, and also in the crypt:villus-tip gradient of maturation. Previous work has studied vitamin D-dependent calcium binding to intestinal Golgi membranes and preliminary studies have shown the presence of ATP-dependent calcium transport in intestinal Golgi membranes. The specific aims of the proposed research are:- (1) preparation of subcellular membrane fractions, and characterization with respect to markers for Golgi, baso-lateral, and endoplasmic reticulum membranes, using cells isolated from (a) proximal or distal segments or rat small intestine, and (b) villus-tip or crypt regions of the segments; (2) determination of ATP-dependent calcimm uptake by these intestinal membrane vesicle fractions, and investigation of factors known in other tissues to be capable of inhibiting or stimulating membrane calcium transport; and (3) investigation of the effects of hormonal agents including 1,25-dihydroxycholecalciferol, and various agents affecting secretion or absorption, on ATP-dependent calcium uptake in membrane vesicles representing different subcellular components. The planned research will be a further step toward the long-term goal of understanding the regulation of intestinal cellular absorptive processes.

本研究的目的是在不同的肠道中描绘 上皮细胞类型、各种亚细胞膜相关机制 来运输钙。这些膜系统可能在 胞质内游离钙和钙离子的生理调节 跨细胞钙吸收。膜钙泵可通过以下途径发挥作用(I) 钙从细胞中排出穿过基底膜，以及 (Ii)通过将钙隔离在细胞内存储位置， 在其他组织中，存在于内质网、线粒体和 高尔基仪器。有证据表明，这些商店涉及到远端 小肠中的荷尔蒙控制水和电解质的分泌 吸收，从而在发病机制和治疗中起重要作用 腹泻病。在近端的小肠，钙泵是 维生素过程中钙跨上皮细胞的转运 D依赖的主动钙吸收等可能与 骨软化和老年性骨质疏松症。计划对这一事件进行调查 亚细胞膜钙转运机制的差异 近端：肠功能的远端梯度，也在 隐窝：绒毛-顶端的成熟梯度。之前的工作是研究维生素 D依赖性钙离子与肠道高尔基膜结合的初步研究 研究表明，心肌细胞存在依赖于ATP的钙转运。 肠道高尔基膜。拟议研究的具体目标 是：-(1)亚细胞膜部分的制备，以及 高尔基体、基侧向和侧向标记的特征 内质网膜，使用从(A)近端或 远端节段或大鼠小肠；(B)绒毛顶端或隐窝区域 (2)这些片段对依赖于ATP的钙摄取的测定 肠膜泡囊组分及其已知因素的研究 在其他组织中能够抑制或刺激膜 钙转运；以及(3)激素剂影响的研究 包括1，25-二羟基胆钙醇，以及各种影响 膜上ATP依赖性钙摄取的分泌或吸收 代表不同亚细胞成分的小泡。计划中的 研究将是朝着理解的长期目标进一步迈进的一步 肠道细胞吸收过程的调节。