The specific aims are to localize and further characterize HCO3- absorption and HCO3- secretion by specific cells of the intestinal mucosa using ion-selective microelectrodes, pH stat and other techniques and to test specific models postulated for HCO3- transport, and the enhanced secretion following exposure to cyclic AMP. The relationship between intracellular pH measured with liquid ion-exchange microelectrodes and HCO3- absorption measured by pH stat will be determined in in vitro segments of Amphiuma jejunum. The postulate that H+ secretion is linked to K+ uptake will be tested in detail and the role of intracellular Na+ in influencing the rate of HCO3- absorption will be assessed with Na+ sensitive microelectrodes. The possibility that acetazolamide, DIDS and cyclic AMP alter HCO3- absorption by changes in intracellular pH will be tested. The role of basolateral Na/H exchange in duodenal HCO3- secretion and the electrogenic secretion induced by theophylline will be investigated with Na+- specific microelectrodes. The effect of cholera toxin on HCO3- secretion as well as HCO3- absorption will be studied in detail. The ion transport underlying the electrically silent secretion of HCO3- induced by secretin and glucagon will be characterized. The influence of different hormones and neurotransmitters on HCO3- transport will be determined. The contribution of villus and intervillus (crypt) regions of the mucosa to HCO3- absorption and secretion will be measured directly by pH stat. Finally brush border membranes will be isolated and assayed for K+, HCO3- and Cl- stimulated ATPase activity. The results of this study will provide a better understanding of the mechanisms and control of K+, CL- and HCO3 absorption and the secretion of HCO3-. From a clinical perspective the studies are important for understanding the etiology of duodenal ulcers as well as diarrheal diseases including cholera and chloride diarrhea.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM026870-06
Application #
3151680
Study Section
Physiology Study Section (PHY)
Project Start
1980-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322