The overall goal of this research is to determine the physiological role of the AE2 anion exchanger in epithelial cells that line the colon and biliary system. AE2 functions to exchange one chloride for one bicarbonate ion across the membrane of many cell types. This activity results in net chloride movement into the cell (where it is available for secretion by other transporters) and net bicarbonate movement out of the cell. In the colon, AE2 has been proposed to mediate chloride uptake into the epithelial cells to support transepithelial secretion and to provide an exit pathway for bicarbonate from the cell during bicarbonate absorption. In the biliary system, AE2 is believed to be expressed on the apical membrane and mediate the electrically-silent component of bicarbonate secretion into bile. Using gene-targeting technology, the aims of this proposal are i) to test the hypotheses that AE2 is critical to chloride and bicarbonate transport in colonic and biliary epithelial cells and 2) develop an intestine-specific AE2 knockout to evaluate the role of AE2 in colonic bicarbonate absorption.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK067749-02
Application #
7054665
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Podskalny, Judith M,
Project Start
2004-05-01
Project End
2006-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
2
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
University of Cincinnati
Department
Physiology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Gawenis, Lara R; Bradford, Emily M; Prasad, Vikram et al. (2007) Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. J Biol Chem 282:9042-52
Gawenis, Lara R; Greeb, Jeannette M; Prasad, Vikram et al. (2005) Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. J Biol Chem 280:12781-9
Gawenis, Lara R; Ledoussal, Clara; Judd, Louise M et al. (2004) Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. J Biol Chem 279:30531-9