HYDROGEN ION REGULATION BY THE MAMMALIAN NEPHRON

哺乳动物肾单位对氢离子的调节

• 批准号: 3483433
• 负责人: RICHARD L TANNEN
• 金额: $ 31.1万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483433
• 关键词: acidity /alkalinity; acidosis; alkalosis; amination; ammonia; dietary potassium; diuretics; dogs; gluconeogenesis; glutamine; homeostasis; hydrogen transport; hypokalemia; hypoxia; ion transport; ketoacid; kidney function; laboratory rat; lactates; mitochondria; perfusion; phosphoenolpyruvate; potassium; renal tubular transport; renal tubule; respiratory acidosis; urine acidity

Our aims during this grant period will be to delineate further the signals, effectors, pathways and rate-limiting biochemical steps for both the acute and adaptive changes in renal ammoniagenesis in response to alterations in H+ and K+ homeostasis. In addition the mechanisms of action of several modulators of ammoniagenesis will be explored, including prostaglandins, calcium, cyclic AMP, glucocorticoids and aldosterone. The major experimental model utilized will be renal epithelium grown in cell culture. The LLC-PK1 continuous pig cell line will be used. In addition primary cultures of rat, dog and human proximal tubular epithelium will be developed and utilized. Techniques employed with cultured cells will include enzyme analysis, measurments of metabolites, pulse chase isotopic studies, investigation of isolated mitochondria, and studies of the molecular biology of adaptation. In addition to cell culture, experiments with intact animals, isolated perfused kidney, renal cortical tubule and isolated mitochondria will be used to address the mechanisms of decreased NH3 production with acute alkalosis, the signal for adaptation to chronic acidosis, the inhibitory effect of PGF2alpha and the K+ sparing effect of increased NH3 production.

我们在此拨款期间的目标将是进一步描绘信号， 急性炎症反应的效应器、途径和限速生化步骤 以及肾氨生成响应于改变的适应性变化 H+ 和 K+ 稳态。 此外，几种药物的作用机制 将探索氨生成调节剂，包括前列腺素， 钙、环磷酸腺苷、糖皮质激素和醛固酮。 使用的主要实验模型将是生长在 细胞培养。 将使用 LLC-PK1 连续猪细胞系。 在 另外，大鼠、狗和人近端肾小管上皮的原代培养物 将得到开发和利用。 培养细胞所采用的技术 将包括酶分析、代谢物测量、脉冲追踪 同位素研究、分离线粒体的研究以及 适应的分子生物学。 除了细胞培养之外，还用完整的动物进行实验，分离 灌注的肾脏、肾皮质小管和分离的线粒体将被 用于解决急性期 NH3 产生减少的机制 碱中毒，适应慢性酸中毒的信号，抑制性 PGF2alpha 的影响和增加 NH3 产生的 K+ 节约效应。