Glycine-extended processing intermediates of gastrin and cholecystokinin in human plasma

The biosynthesis of biologically active gastrin and cholecystokinin (CCK) requires the formation of carboxyl-terminally amidated peptides from glycine-extended precursors of gastrin and CCK. In previous studies we and others have identified and characterized glycine-extended forms of gastrin (Ggly) and CCK (CCK-gly) in the human gastrointestinal tract. To explore the potential biologic importance of these peptides in humans, we examined their release into the circulation. Ingestion of a standard meal induced a biphasic rise in plasma G/CCK-gly concentration, but only the initial increase correlated with gastrin release. Intraduodenal lipid infusion caused a selective rise in CCK-gly immunoreactivity with no increase in gastrin or G-gly. Gel filtration chromatography revealed that the predominant molecular form of G/CCK-gly in basal plasma coeluted with CCK8-gly, but in response to meal stimulation, increases in other molecular forms were noted. Measurement of glycine-extended intermediates of progastrin and procholecystokinin posttranslational processing in plasma may aid in determining their physiologic importance in health and disease.