Abstract

The proposed research is to elucidate the molecular basis of the facilitated sodium entry mechanism which exists in the outer (or apical) membrane of all tight epithelial tissues. This sodium entry step is an essential component of the overall active transport system responsible for the net movement of salt and water across these structures. This entry process is passive, and is sensitive to inhibition by the diuretic drug, amiloride. The analysis of the mechanism of Na entry encompasses determinations of cation selectivities, the effects of chemical group-specific reagents and other pharmacological substances on Na entry and amiloride efficiency, a determination of site number from binding studies of a photosensitive amiloride analogue (bromoamiloride), and the preparation of membrane vesicles containing functional Na-entry sites. A comparative approach, utilizing the isolated amphibian skin and bladder preparations as well as the isolated rabbit colon, will be taken. These studies will contribute to our knowledge of the kinetic and biochemical properties of epithelial transport systems and increase our comprehension of the mode of action of amiloride and other diuretic compounds.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037206-02
Application #
3235974
Study Section
Physiology Study Section (PHY)
Project Start
1985-09-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
School of Medicine & Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Reddy, Bharat G; Dai, Qun; McNicholas, Carmel M et al. (2016) Expression and purification of the alpha subunit of the epithelial sodium channel, ENaC. Protein Expr Purif 117:67-75
Rooj, Arun K; Liu, Zhiyong; McNicholas, Carmel M et al. (2015) Physical and functional interactions between a glioma cation channel and integrin-?1 require ?-actinin. Am J Physiol Cell Physiol 309:C308-19
Fuller, Catherine M; Insel, Paul A (2014) I don't know the question, but sex is definitely the answer! Focus on ""In pursuit of scientific excellence: sex matters"" and ""Do you know the sex of your cells?"". Am J Physiol Cell Physiol 306:C1-2
Qadri, Yawar J; Rooj, Arun K; Fuller, Catherine M (2012) ENaCs and ASICs as therapeutic targets. Am J Physiol Cell Physiol 302:C943-65
Rooj, Arun K; McNicholas, Carmel M; Bartoszewski, Rafal et al. (2012) Glioma-specific cation conductance regulates migration and cell cycle progression. J Biol Chem 287:4053-65
Fuller, Cathy M (2012) Time for TMEM? J Physiol 590:5931-2
Qadri, Yawar J; Cormet-Boyaka, Estelle; Rooj, Arun K et al. (2012) Low temperature and chemical rescue affect molecular proximity of DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC). J Biol Chem 287:16781-90
Bartoszewski, Rafal; Brewer, Joseph W; Rab, Andras et al. (2011) The unfolded protein response (UPR)-activated transcription factor X-box-binding protein 1 (XBP1) induces microRNA-346 expression that targets the human antigen peptide transporter 1 (TAP1) mRNA and governs immune regulatory genes. J Biol Chem 286:41862-70
Kapoor, Niren; Lee, William; Clark, Edlira et al. (2011) Interaction of ASIC1 and ENaC subunits in human glioma cells and rat astrocytes. Am J Physiol Cell Physiol 300:C1246-59
Qadri, Yawar J; Cormet-Boyaka, Estelle; Benos, Dale J et al. (2011) CFTR regulation of epithelial sodium channel. Methods Mol Biol 742:35-50

Showing the most recent 10 out of 121 publications