William A. Bolhofer

Chapter 10. Agents Affecting Gastrointestinal Functions

Publisher Summary In humans, gastrin is 80-fold more potent than histamine in stimulating secretion. Currently, the major clinical use of gastrin or active fragments would appear to be for the replacement of histamine and other secretagogues for the diagnostic analysis of gastric secretions. Gastrin exerts a stimulatory and inhibitory effect on acid secretion at low and high doses, respectively, and a stimulatory effect on pepsin secretion at high doses, regardless of whether the initial stimulation was histamine or gastrin. However, it has been suggested that stimulation was the normal effect and inhibition was the result of overdosage. The histamine content of the stomach mucosa is decreased by gastrin, indicating that it may act as a secretory agent by releasing histamine. Acid secretion stimulated by exogenous gastrin is inhibited by heparin and by insulin hypoglycemia. A major advance in the biochemistry of gastric secretion has been made with the determination of the structure and synthesis of gastrin I and II from various species. Porcine gastrin I has been shown to be the heptadecapeptide I. Porcine gastrin II has the same peptide sequence but with the tyrosine hydroxyl in the form of its sulfate ester. The pure human gastrins have been isolated, and degradative analysis and total synthesis showed that human gastrin I and human gastrin II are heptadecapeptides identical to the porcine gastrins except for replacement of one of the methionine components by leucine. The porcine gastrins stimulated secretion in other species including dogs and man.