Approximately 16 million Americans alive today will develop ulcer disease and many others will develop other acid-peptic diseases (e.g. espphagitis, gastritis). The economic impact of acid-peptic diseases is tremendous. For example, 3-5 billion dollars per year is spent on treatment of ulcer disease in the United States. In most patients, the cause of peptic ulcer disease is unknown although, in general, it is believed to be related to an imbalance between aggressive, luminal factors such as acid and pepsin and mucosal protective mechanisms such as bicarbonate and prostaglandins. The specific goals of the research described in this application are to study mechanisms of gastric acid secretion and release of hormones that regulate acid secretion in humans with, or without, peptic ulcer disease; to study the effects of surgical vagotomy on gastric acid secretion in patients with duodenal ulcer or with Zollinger-Ellison syndrome; to determine whether two classes of pharmacologic agents, a GABA agonist (progabide) or beta-adrenergic agonists (isoproterenol or terbutaline) reduce gastric acid secretion in humans and animals; to compare soy protein with meat protein as stimulants for acid secretion; to study gastric and duodenal HCO3 secretion; to clarify the role of prostaglandins in peptic ulcer disease in man and in animals; and to determine whether infection with campylobacter-like organisms is related to gastric mucusal diseases in humans or dogs. Several methods will be used to measure acid secretion: aspiration via a nasogastric tube (humans), collection of gastric juice through a fistula (dogs); in vivo intragastric titration (meal studies in humans); and in vitro titration of fluid after perfusion through the gastric lumen (rats). Sham feeding will be used to activate vagally-mediated acid secretion in humans and dogs. Titration methods will be used to measure duodenal HCO3ion secretion and jejunal HCO3ion absorption. Prostaglandins will be measured by high pressure liquid chromatography and by radioimmunoassay. Campylobacter gastritis will be studied by microbiological culture methods and by light and electron microscopy. Thus, this research will focus primarily on the role of gastric acid, mucosal defense factors (bicarbonate, prostaglandins) and a campylobacter-like bacterium on acid-peptic diseases.
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