The intestinal phase hormone.

The existence of a stimulatory intestinal phase of gastric acid secretion has been suspected, but largely ignored, for many years. Recently, however, it has become clear that the intestinal phase plays an important role in acid production during digestion. The intestinal phase is of additional interest in relation to the profound gastric acid hypersecretion associated with portacaval shunt (PCS). Substantial evidence indicates that PCS-related gastric hypersecretion is due to unmasking of the intestinal phase by hepatic bypass of a humoral stimulant in portal blood that is normally degraded to a considerable extent by the liver. Studies in our laboratory during the past 12 years have provided strong physiologic evidence for humoral mediation of both the intestinal phase of gastric secretion and of PCS-related hypersecretion by a hormone that arises in the small intestine, particularly in the jejunum. Furthermore, our studies have demonstrated that this intestinal phase hormone (IPH) exists in humans as well as in dogs, rats, and pigs. Additionally, recent work by a number of investigators, as well as by our group, has provided convincing evidence that IPH is different from any of the known gastric stimulatory hormones. With these physiologic observations as a background, we have used a classical method for extracting acidic peptides to prepare a hog intestinal mucosa extract (HIME) that has all of the known physiologic properties of an IPH. Specifically, HIME contains a potent stimulant of gastric acid secretion that acts according to a linear dose-response relationship; that is not gastrin in any of its immunoassayable forms; that significantly augments the maximal acid secretory responses to pentagastrin, gastrin, CCK, and histamine; and that is substantially degraded by the liver, in contrast to gastrin and CCK. Efforts at isolating the gastric stimulatory substance in HIME suggest that it is a peptide of low molecular weight. Work directed at isolating IPH in pure form and identifying it is in progress.