Abnormally processed gastrins in active duodenal ulcer disease

Abstract

In contrast to healthy subjects, duodenal ulcer patients in the active phase contain large amounts of a peptide in serum and antrum which react with antiserum specific for the N-terminus, but not the C-terminus of gastrin-17. The immunochemical and chromatographic properties were similar to that of the N-terminal tridecapeptide sequence of gastrin-17. The peptide follows the clinical course of duodenal ulcer disease, as it disappears when the ulcer heals. The N-terminal tridecapeptide - lacking the bioactive tetrapeptide of gastrin-17 - is a potent inhibitor of gastric acid secretion, presumably by way of competitive antagonism to gastrin. It is suggested to participate in the regulation of gastric acid secretion in patients with active duodenal ulcer disease. To confirm the chemical structure of the peptide, antral and gastrinoma extracts were used for isolation, purification and amino acid analysis. We found two different peptides with the same N-terminus as gastrin-17, namely the previously known N-terminal tridecapeptide fragment of gastrin-17 and a new gastrin component, identical with a C-terminal glycine extended gastrin-17. Furthermore, a C-terminal glycine extended component, corresponding to each of the other molecular forms of gastrin were present. Thus, a variety of abnormally processed gastrins are synthesized and released to the circulation during the active period of duodenal ulcer disease.