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.
| 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 |
