Measurement and occurrence of sulfated gastrins.

Abstract

Sulfated gastrins resemble cholecystokinins (CCK) both structurally and functionally. They are less potent than CCK in stimulating gallbladder contraction and pancreatic enzyme secretion, but the plasma concentrations of sulfated gastrin are higher than those of CCK. Therefore, sulfated gastrins may contribute significantly to the endogenous CCK activity. The degree of sulfation of gastrin differs with the localization in the digestive tract. In the antrum and duodenum of normal subjects 45% of the gastrins are sulfated, as in serum. In contrast, the sulfation of gastrin is complete in the jejunum (human) and in the pancreas (rat and cat). Hence, the degree of sulfation of gastrin is similar to that of CCK in the jejunum. The degree of sulfation in antrum, duodenum and serum diminishes with hypergastrinemia, and is thus significantly lower in patients with gastric ulcer or pernicious anemia than in healthy subjects. In the Zollinger-Ellison syndrome, the degree of sulfation of gastrin varies greatly (20-90%) and the distribution between small and large gastrins is equally variable. However, sulfation and proteolytic processing follows a parallel course; complete processing to smaller components is accompanied by complete sulfation of the peptide and vice versa. During ontogenesis sulfated gastrins may be of special importance, since they are the only sulfated members of the gastrin/CCK family of peptides which occur in substantial quantities in the early fetus. Tyrosine-O-sulfation has now been recognized as a widespread modification, and sulfated tyrosyl residues in gastrin, CCK and leu-enkephalin are examples of a derivatization which can govern the biological activity of regulatory peptides.