Ammonia plays a central role in acid-base homeostasis. It is produced by the proximal tubule, concentrated in the renal interstitium by the loop of Henle and excreted into the urine in the collecting duct. The production and excretion of ammonia results in equimolar production of new bicarbonate molecules, thereby allowing ammoniagenesis and excretion to contribute to acid-base homeostasis. Recent studies show that ammonia has additional functions that are completely independent of its role as a urinary constituent. These studies show that ammonia stimulates CCD net bicarbonate reabsorption through stimulation of H,K-ATPase. Thus, the increased ammonia that results from metabolic acidosis and hypokalemia may result in feedback stimulation of H,K-ATPase-mediated proton secretion and potassium reabsorption. The purpose of the proposed studies is to increase our understanding of the mechanisms through which ammonia increases CCD net bicarbonate reabsorption.
The Specific Aims through which these plans will pursue this overall goal are: 1) to define the specific transporters regulated by ammonia that effect the changes in proton secretion and net bicarbonate reabsorption; 2) to define the basic signaling mechanisms through which ammonia regulates these transporters, with specific emphasis on the calcium-calmodulin, MAPK and microtubule-dependent pathways; and, 3) to define whether the chronic effects of ammonia are related to stimulation of protein expression or through inhibition of cathepsin-mediated protein degradation.
| Harris, Autumn N; Grimm, P Richard; Lee, Hyun-Wook et al. (2018) Mechanism of Hyperkalemia-Induced Metabolic Acidosis. J Am Soc Nephrol 29:1411-1425 |
| Harris, Autumn N; Lee, Hyun-Wook; Osis, Gunars et al. (2018) Differences in renal ammonia metabolism in male and female kidney. Am J Physiol Renal Physiol 315:F211-F222 |
| Lee, Hyun-Wook; Osis, Gunars; Harris, Autumn N et al. (2018) NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic Acidosis. J Am Soc Nephrol 29:1182-1197 |
| Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E et al. (2017) Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction. Am J Physiol Renal Physiol 313:F116-F125 |
| Weiner, I David; Verlander, Jill W (2017) Ammonia Transporters and Their Role in Acid-Base Balance. Physiol Rev 97:465-494 |
| Lee, Hyun-Wook; Handlogten, Mary E; Osis, Gunars et al. (2017) Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney. Am J Physiol Renal Physiol 312:F427-F435 |
| Weiner, I David (2017) Roles of renal ammonia metabolism other than in acid-base homeostasis. Pediatr Nephrol 32:933-942 |
| Canales, Benjamin K; Smith, Jennifer A; Weiner, I David et al. (2017) Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH. Kidney Int Rep 2:1111-1121 |
| Osis, Gunars; Handlogten, Mary E; Lee, Hyun-Wook et al. (2016) Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling. Physiol Rep 4: |
| Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E et al. (2016) Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism. Am J Physiol Renal Physiol 310:F1229-42 |
Showing the most recent 10 out of 39 publications
