This research is directed at an understanding of the mechanisms of H+ and Cl- transport by gastric mucosa. In recent years there has been great interest in the importance of the gastric (H++K+) ATPase as the primary gastric H+ pump, and the rather profound changes in membrane structure and transport function as the gastric oxyntic cells are stimulated to secrete hydrochloric acid. Normal physiological function of these cellular processes are essential for a healthy for a healthy stomach and effective digestion. The proposed research is developed within three major sections, based on the theme of principal questions being addressed. The first section examines the cell biology of the oxyntic cell in terms of the nature and regulation of membrane changes associated with HCl secretion. This will include an assessment of the morphological and functional changes in secretory membranes through all stages of physiological activity. The membranes will be isolated and characterized according to composition and transport activity. The mechanisms of cell and membrane activation will be studied through an examination of regulatory steps, such as membrane phosphorylation, as well as the role of cytoskeletal elements in regulating oxyntic cell form and menbrane transformations. The second section deals with a detailed analysis of the transport properties of isolated gastric membrane vesicles that are rich in (H++K+) ATPase. The major objectives here are to assess the mechanisms by which K+ and Cl- are transported when the membranes are """"""""activated"""""""" in the normal course of gastric stimulation. This research will also define the ways in which the systems of activated K+ and Cl- transport interdigitate with the H+/K+ exchange pump enzyme. The third section concentrates on the (H++K+) ATPase. These experiments will study detailed kinetics of the gastric pump enzyme. They are designed to elucidate the catalytic cycle of the enzyme and the nature of the principal energy translocation step in the cycle.
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