INTRACELLULAR REACTIONS IN GASTRIC MUCOSA

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The longterm goal of this program is to describe the sequence of cellular reactions which lead to the secretion of hydrochloric acid by the gastric mucosa with emphasis on those reactions which serve as the major controlling steps. Recent interest in this area derives from the success of antisecretory agents in the clinical management of ulcer disease and the appreciation of the important role of proton transport in various biological processes. The current proposal seeks to extend previous observations concerning the cellular control of acid secretion so as to provide a more detailed understanding of the control mechanisms. Projects will utilize the recently developed preparations of isolated gastric glands and digitonin-permeabilized cells as well as the more traditional amphibian gastric mucosa as in vitro models. A combination of modern biophysical, biochemical, and morphological techniques will be used to investigate selected aspects of cellular control mechanisms. The major areas to be investigated include: 1) regulation of histamine H2-receptor; 2) the role of protein kinases, specifically the cAMP-dependent and calcium/phospholipid-dependent enzymes; 3) the basic mechanisms involved in the morphological transition of the parietal cell which occurs with stimulation; 4) the relationship between mitochondrial metabolism and proton transport; and 5) the effects of omeprazole, an H-KATPase inhibitor, on ion transport mechanisms. These areas are identified as important regulatory sites, the investigation of which are timely and promises a high rate of progress towards the longterm goal.