During the past decade, the most important contribution to the study of gastric secretion was the isolation, characterization and synthesis of the antral hormone gastrin. Recently, radioimmunoassay techniques have been devised for the measurement of gastrin. We will utilize these and other techniques to develop in vitro models for the study of the action, synthesis and secretion of gastrin. We will use isolated gastric fundus mucosa (frog, dog, rat and human) to study the action of gastrin on acid and pepsin secretion and on the other cellular and subcellular events which occur in relation to the secretion of acid and pepsin. In particular, we will study gastrin induced changes in RNA, DNA and protein (pepsin) synthesis. We will also measure the gastrin stimulated metabolism of C14-labeled substrates. A major goal will be to determine whether the reactivity of normal gastric mucosa differs from that of peptic ulcer patients. Using the isolated gastric antrum (hog, dog, human, rat, frog) and Zollinger-Ellison (Z-E) tumor tissue, we will develop in vitro models for the de novo synthesis (measured by C14-glutamate incorporation) and secretion (measured by radioimmunoassay of gastrin. We will also study metabolic events in antrum and tumor associated with gastrin secretion, eg. RNA, DNA, protein synthesis and substrate oxidation. Particular emphasis will be placed on the study of human antral mucosa (normal and peptic ulcer). We will also compare human antral mucosa with Z-E tumor with respect to gastrin secretion (stimulated by acetylcholine, Ca ions). The tissue storage form of gastrin is unknown. We will attempt to determine by immunoassay techniques and column chromatography whether tissue gastrin differs from synthetic gastrin. We will also determine the phylogeny of gastrin, i.e. its appearance and concentration in antra of other species, especially lower vertebrates. We will also provide a diagnostic service for Western U.S. clinicians by measuring serum gastrin in patients with suspected Z-E syndrome.