The primary objective of the studies outlined in this proposal is to elucidate more fully the overall role of the kidney in systemic acid-base homeostais. During previous years studies have been designed to investigate the basic mechanism(s) responsible for urinary acidification and the regulation of this process in several nephorn segments, the maintenance of elevated CO2 tensions in the renal cortex, and the utility of urinary COs tension as a qualitative index of H+ secretion by the terminal nephron. The present application proposes to continue our investigation of fundamental mechanisms of the acidification process, but places major emphasis on investigation of the mechanism of impaired urinary acidification in experimental models of deranged acid- base and/or electrolyte balance. In order to accomplish these goals four specific projects are proposed: 1) Evaluation of acidification parameters in experimental models of distal renal tubular acidosis and selective aldosterone deficiency. 2) Evaluation of segmental ammonia transport in medullary and cortical nephrons to determine the role of ammonia transfer from the loop of Henle to the collecting duct in urinary ammonium excretion during changes in systemic potassium balance, mineralocorticoid deficiency and ureteral obstruction. 3) Evaluation of the role of transepithelial pH gradients in the regulation of H+ secretion by the proximal convoluted tubule. 4) Evaluation of the mechanism and kinetics of H+ secretion in human brush border membrane vesicles in vitro and to compare these findings with other mammaliam species. An important advantage of the in vivo micropuncture studies proposed in this application is the capability in our laboratory of extending these observations by investigation similar questions in the isolated perfused tubule in vitro. The maintenance of acid-base balance is an essential physiological role of the kidney. The control of this process must be understood to fully elucidate these functions. The study of models of deranged acidification, such as renal tubular acidosis, may enhance our understanding of this disease in humans, and improve our ability to diagnose this condition early in the course of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030603-12
Application #
3229560
Study Section
General Medicine B Study Section (GMB)
Project Start
1981-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1993-06-30
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Fisher, Kimberly D; Codina, Juan; Petrovic, Snezana et al. (2012) Pyk2 regulates H+-ATPase-mediated proton secretion in the outer medullary collecting duct via an ERK1/2 signaling pathway. Am J Physiol Renal Physiol 303:F1353-62
Codina, Juan; Opyd, Timothy S; Powell, Zachary B et al. (2011) pH-dependent regulation of the ýý-subunit of H+-K+-ATPase (HKýý2). Am J Physiol Renal Physiol 301:F536-43
Codina, Juan; DuBose Jr, Thomas D (2006) Molecular regulation and physiology of the H+,K+ -ATPases in kidney. Semin Nephrol 26:345-51
Codina, Juan; Liu, Jingfang; Bleyer, Anthony J et al. (2006) Phosphorylation of S955 at the protein kinase A consensus promotes maturation of the alpha subunit of the colonic H+,K+ -ATPase. J Am Soc Nephrol 17:1833-40
Codina, Juan; Li, Jian; Dubose Jr, Thomas D (2005) CD63 interacts with the carboxy terminus of the colonic H+-K+-ATPase to decrease [corrected] plasma membrane localization and 86Rb+ uptake. Am J Physiol Cell Physiol 288:C1279-86
Li, Jian; Codina, Juan; Petroske, Elizabeth et al. (2004) The effect of beta-subunit assembly on function and localization of the colonic H+,K+-ATPase alpha-subunit. Kidney Int 66:1068-75
Codina, Juan; Li, Jian; Dubose Jr, Thomas D (2004) A carboxy-terminus motif of HKalpha2 is necessary for assembly and function. Kidney Int 66:2283-92
Li, Jian; Codina, Juan; Petroske, Elizabeth et al. (2004) The carboxy terminus of the colonic H(+), K(+)-ATPase alpha-subunit is required for stable beta subunit assembly and function. Kidney Int 65:1301-10
Codina, Juan; Li, Jian; Hong, Yan et al. (2002) The gamma-Na+,K+-ATPase subunit assembles selectively with alpha1/beta1-Na+,K+-ATPase but not with the colonic H+,K+-ATPase. Kidney Int 61:967-74
DuBose Jr, T D (2000) Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis. Trans Am Clin Climatol Assoc 111:122-33; discussion 133-4

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