Hydrochloric acid secretion by the gastric parietal cell involves major membrane rearrangements. Stimulation triggers translocation of the H+/K+-ATPase proton pump from the intracellular compartment of tubulovesicles, leading to fusion of the vesicles with the apical/canalicular membrane. While the exact pathway of activation is not known, protein kinases are believed to be involved. The overall object of this proposal is to elucidate the nature of the signaling events that occur in the early stages of parietal cell activation, and the manner in which these events effect, and are dependent upon, the actin cytoskeleton. Toward this goal, several parietal cell models will be employed that allow access to, or manipulation of, the intracellular contents of the parietal cell. The effects of certain protein kinase inhibitors actin binding substances on acid secretion and cytoskeletal rearrangement will be determined. Elucidating the control mechanisms of HC1 secretion is fundamental for treatment of medical conditions of the stomach. These conditions range from minor issues, such as dyspepsia and gastritis, to life-threatening conditions, such as gastric and esophageal cancer.

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 #
5F32DK009984-03
Application #
6402565
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Podskalny, Judith M,
Project Start
2001-09-01
Project End
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$41,996
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Ammar, David A; Zhou, Rihong; Forte, John G et al. (2002) Syntaxin 3 is required for cAMP-induced acid secretion: streptolysin O-permeabilized gastric gland model. Am J Physiol Gastrointest Liver Physiol 282:G23-33
Ammar, D A; Nguyen, P N; Forte, J G (2001) Functionally distinct pools of actin in secretory cells. Am J Physiol Cell Physiol 281:C407-17