SOLUTE AND WATER TRANSPORT IN RENAL EPITHELIA

肾上皮中的溶质和水运输

• 批准号: 3920033
• 负责人: M A KNEPPER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3920033
• 关键词: ammonia; ammonium compounds; atrial natriuretic peptide; biological fluid transport; body fluid osmolarity; body water; chlorine; cyclic AMP; electrolyte balance; epithelium; excretion; hormone regulation /control mechanism; ion transport; kidney pharmacology; laboratory rabbit; laboratory rat; potassium; renal tubular transport; saluresis; sodium chloride; urea; vasopressins

The kidney contains several distinct epithelia that, in their aggregate function, are responsible for formation of the urine. We are studying the roles of these epithelia in the regulation of the excretion of water, urea, ammonium, bicarbonate, sodium, potassium, and chloride. The general approach is to dissect the epithelia from the kidney and to study their functions in vitro. Experiments in the cortical collecting duct of rat showed that atrial natriuretic factor (ANF) directly inhibits NaCl and fluid absorption. Experiments in rat inner medullary collecting ducts revealed that ANF markedly inhibits vasopressin-stimulated osmotic water permeability by a "post-cyclic AMP" effect. Mathematical modelling studies have demonstrated that ANF effects in the collecting duct system are quantitatively sufficient to account for increases in renal NaCl and fluid excretion. Isolated perfused tubule studies have demonstrated that vasopressin-stimulated urea transport in the rat inner medullary collecting duct is saturable, is inhibited by chemical analogs of urea, is inhibited by phloretin, and is independent of the vasopressin-stimulated water permeability pathway. These results support the view that the urea transport occurs via a specialized urea carrier or channel. Experiments in terminal inner medullary collecting ducts have demonstrated luminal acidification, which is increased by in vivo acidosis or deoxycorticosterone administration and by vasopressin in vivo. Experiments in microdissected rat collecting ducts have demonstrated that the terminal inner medullary collecting duct possesses substantial Na-K-ATPase activity which is enhanced by dietary NaCl restriction or mineralocorticoid administration. Experiments in isolated rabbit papillary surface epithelium have demonstrated that vasopressin reduces passive chloride permeability.

肾脏含有几种不同的上皮细胞，它们的 聚集功能，负责尿液的形成。 我们正在研究这些上皮细胞在调节中的作用 水、尿素、铵、碳酸氢盐、钠的排泄， 钾和氯化物。 一般的方法是剖析 肾上皮细胞并在体外研究其功能。 大鼠皮质集合管实验表明 心房钠尿因子 (ANF) 直接抑制 NaCl 和液体 吸收。 大鼠内髓集合管实验 揭示 ANF 显着抑制加压素刺激的渗透压 水渗透性受“后环AMP”效应影响。 数学 模型研究表明，ANF 对 集合管系统的数量足以解释 肾脏 NaCl 和液体排泄增加。 隔离灌注 肾小管研究表明，加压素刺激的尿素 大鼠内髓集合管中的运输是饱和的， 被尿素的化学类似物抑制，被抑制 根皮素，并且独立于加压素刺激的水 通透性途径。 这些结果支持尿素的观点 运输通过专门的尿素载体或通道进行。 终末内髓集合管实验 证明管腔酸化，体内增加 酸中毒或去氧皮质酮给药以及加压素 体内。 显微解剖大鼠集合管实验 证明了终末内髓集合管 具有显着的 Na-K-ATP 酶活性，其增强 饮食中氯化钠限制或盐皮质激素给药。 离体兔乳头表面上皮实验 证明加压素可减少被动氯化物 渗透性。