Abstract

The control of acid-base regulation by the kidney is critical in maintaining body electrolyte homeostasis and acid secretion is a cornerstone of this function. The specific purposes of this proposal are to examine the cellular mechanisms and modulators of acid secretion in cultured cells derived from the inner medullary collecting duct of the rat kidney. This cell culture line provides an excellent model for the study of distal epithelial cell acid-base function since these cells contain many, if not all, of the acid-base transporters that regulate distal protein secretion. Thus, this culture cell system provides a unique opportunity for determining the cellular signals that modify these transporters. To this end, techniques including fluorescent probes for monitoring cell pH and calcium, immunohistochemistry, protein electrophoresis, immunoblot, Northern blood and cofocal microscopy will be utilized. The intracellular events which are activated during acid secretion will be studied. These include the interrelationship among cell calcium, cell pH and acid secretion; the protein systems involved in acid secretion, i.e., H+-ATPase, carbonic anhydrase and the anion exchanger; the vesicle system necessary for acid secretion and its control including the cytoskeleton; the mechanisms of acidification adaption; and transepithelial transport. These studies will provide significant new information regarding the cellular mechanisms of acid secretion. Elucidation of the cellular mechanisms which occur in response to perturbations in acid-base status will provide invaluable information in helping to understand cellular transport mechanisms and the pathophysiology and management of acid-base disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028164-19
Application #
2458727
Study Section
Physiology Study Section (PHY)
Program Officer
Scherbenske, M James
Project Start
1988-09-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1999-07-31
Support Year
19
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Boston Health and Hospitals Department
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Banerjee, A; Li, G; Alexander, E A et al. (2001) Role of SNAP-23 in trafficking of H+-ATPase in cultured inner medullary collecting duct cells. Am J Physiol Cell Physiol 280:C775-81
Alexander, E A; Brown, D; Shih, T et al. (1999) Effect of acidification on the location of H+-ATPase in cultured inner medullary collecting duct cells. Am J Physiol 276:C758-63
Banerjee, A; Shih, T; Alexander, E A et al. (1999) SNARE proteins regulate H(+)-ATPase redistribution to the apical membrane in rat renal inner medullary collecting duct cells. J Biol Chem 274:26518-22
Obrador, G; Yuan, H; Shih, T M et al. (1998) Characterization of anion exchangers in an inner medullary collecting duct cell line. J Am Soc Nephrol 9:746-54
Alexander, E A; Shih, T; Schwartz, J H (1997) H+ secretion is inhibited by clostridial toxins in an inner medullary collecting duct cell line. Am J Physiol 273:F1054-7
Schwartz, J H (1995) Renal acid-base transport: the regulatory role of the inner medullary collecting duct. Kidney Int 47:333-41
Schwartz, J H; Masino, S A; Nichols, R D et al. (1994) Intracellular modulation of acid secretion in rat inner medullary collecting duct cells. Am J Physiol 266:F94-101
Schwartz, G J; Brown, D; Mankus, R et al. (1994) Low pH enhances expression of carbonic anhydrase II by cultured rat inner medullary collecting duct cells. Am J Physiol 266:C508-14
Mankus, R; Schwartz, J H; Alexander, E A (1993) Acidification adaptation in cultured inner medullary collecting duct cells. Am J Physiol 264:F765-9
Slotki, I; Schwartz, J H; Alexander, E A (1993) Interrelationship between cell pH and cell calcium in rat inner medullary collecting duct cells. Am J Physiol 265:C432-8

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