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NACL TRANSPORT IN MEDULLARY THICK LIMB OF HENLE'S LOOP

亨利氏环髓质粗肢中的 NACL 运输

基本信息

批准号：
3152119
负责人：
JILL L EVELOFF
金额：
$ 10.51万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
1983-07-01 至 1986-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152119
关键词：
apical membrane basolateral membrane cell membrane diuretics excretion furosemide ion transport membrane permeability ouabain renal tubular transport stoichiometry

项目摘要

The renal thick ascending limb of Henle's loop (TALH) transports chloride actively against its electrochemical potential gradient. Its movement is inhibited by ouabain, the 'loop' diuretics such as furosemide and its movement appears to be coupled to the movement of sodium across the luminal membrane via a sodium-chloride cotransport system. Although sodium-chloride cotransport systems have been extensively described in mammalian epithelia as the small intestine, gall bladder and trachea by electrophysiological measurements, recently studies using plasma membrane vesicles have cast doubt on whether a direct coupling of sodium and chloride fluxes really exists or whether a 'loose' coupling via Na/H and Cl/OH exchange mechanisms occurs. Thus, this project proposes to investigate the mechanisms of sodium and chloride transport in the medullary TALH. The transport mechanisms for sodium and chloride entry into the cell will be defined by conducting flux studies in isolated TALH cells and in luminal plasma membrane vesicles prepared from these cells. These studies will investigate whether a dependency of sodium on chloride fluxes and conversely a dependency of chloride on sodium fluxes can be demonstrated. This is an essential criterium for the proof of a cotransport system. The characteristics of the sodium-chloride cotransport system will be studied including its localization within the cellular envelope, the anion and cation specificity, the sensitivity to a variety of diuretics and the role of potassium in the cotransport system. The stoichiometry of the cotransport system will be studied in order to elucidate the origin of the lumen-positive potential difference which exists in the intact tubule. Additionally, the kinetic parameters of the cotransport system will be measured in order to define quantitatively the molecular characteristics of the transport system. Through the results of this study the mechanisms and biochemical properties of the sodium-chloride cotransport system, and thus the process of urinary concentration, will be better understood.

肾厚的亨利氏袢升支（TALH）转运氯离子积极对抗其电化学电位梯度。其运动受到哇巴因的抑制，“袢”利尿剂如呋塞米及其运动似乎与钠穿过管腔的运动相耦合膜通过钠-氯化物共转运系统。虽然氯化钠共转运系统已经在哺乳动物上皮细胞如小肠、胆囊和气管，电生理测量，最近的研究使用质膜囊泡使人们怀疑钠和氯化物通量是否真的存在，或者是否通过Na/H和发生Cl/OH交换机制。因此，本项目建议研究了钠离子和氯离子转运的机制，髓质TALH。钠和氯离子进入的转运机制将通过在分离的TALH中进行通量研究来定义细胞和由这些细胞制备的管腔质膜囊泡中。这些研究将调查钠对氯化物的依赖性通量和相反的氯离子对钠通量的依赖性，演示。这是一个证明的基本标准，共运输系统钠-氯共转运的特点系统将进行研究，包括其在蜂窝内的定位包膜、阴离子和阳离子特异性，对多种利尿剂和钾在共转运系统中的作用。的将研究共转运系统的化学计量，阐明了流明正电位差的起源，存在于完整的肾小管中。此外，动力学参数的将测量共转运系统，以定量定义运输系统的分子特征。通过结果，本文研究了氯化钠的作用机理和生化特性，共转运系统，因此尿浓度的过程，将是更好地理解。