Variations in the rate of net acid excretion by the mammalian kidney contribute importantly to the homeostatic regulation of systemic arterial pH. The thick ascending limb of Henle's loop has been recognized only recently as an important site involved in urinary acidification. This nephron segment contributes directly to the renal excretion of net acid by reabsorbing bicarbonate. In addition, the thick ascending limb reabsorbs ammonia, a process which may facilitate transfer of buffer to the collecting ducts and promote urinary acid excretion. No direct information is available regarding the regulation of these transport processes. Therefore, our goal is to examine factors that may contribute to the regulation of ammonia and bicarbonate transport in the cortical and medullary thick ascending limb of the rat. The isolated, perfused tubule technique will be used to investigate four specific issues: I.) The potassium-dependence of thick ascending limb ammonia and bicarbonate transport, II.) The role of chloride in thick ascending limb bicarbonate and ammonia transport, III.) The effects of changes in acid-base balance in vivo on thick ascending limb bicarbonate and ammonia transport in vitro, and IV.) The role of hormones in regulation of thick ascending limb acid-base transport. These specific factors have been chosen because each is known to have important impact on renal acid excretion and because changes in potassium balance, chloride balance and systemic hormone levels are commonly altered during clinical acid-base disorders. These experiments will be the first to examine directly regulation of acid-base transport in the mammalian thick ascending limb. The results should provide important new information regarding the contribution of the thick ascending limb to changes in renal acid excretion associated with a variety of pathological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK001745-03
Application #
3072500
Study Section
General Medicine B Study Section (GMB)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Watts 3rd, B A; Good, D W (1994) Effects of ammonium on intracellular pH in rat medullary thick ascending limb: mechanisms of apical membrane NH4+ transport. J Gen Physiol 103:917-36
Good, D W (1994) Ammonium transport by the thick ascending limb of Henle's loop. Annu Rev Physiol 56:623-47
Watts 3rd, B A; Good, D W (1994) Apical membrane Na+/H+ exchange in rat medullary thick ascending limb. pH-dependence and inhibition by hyperosmolality. J Biol Chem 269:20250-5
Good, D W (1993) The thick ascending limb as a site of renal bicarbonate reabsorption. Semin Nephrol 13:225-35
DuBose Jr, T D; Good, D W (1992) Chronic hyperkalemia impairs ammonium transport and accumulation in the inner medulla of the rat. J Clin Invest 90:1443-9
Beach, R E; Good, D W (1992) Effects of adenosine on ion transport in rat medullary thick ascending limb. Am J Physiol 263:F482-7
Good, D W (1992) Effects of osmolality on bicarbonate absorption by medullary thick ascending limb of the rat. J Clin Invest 89:184-90
DuBose Jr, T D; Good, D W; Hamm, L L et al. (1991) Ammonium transport in the kidney: new physiological concepts and their clinical implications. J Am Soc Nephrol 1:1193-203
DuBose Jr, T D; Good, D W (1991) Effects of chronic hyperkalemia on renal production and proximal tubule transport of ammonium in rats. Am J Physiol 260:F680-7
DuBose Jr, T D; Good, D W (1991) Role of the thick ascending limb and inner medullary collecting duct in the regulation of urinary acidification. Semin Nephrol 11:120-8

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