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.
DelValle
J
J
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Sugano
K
K
Yamada
T
T
D000328:Adult; D002766:Cholecystokinin / Q000096:biosynthesis* / Q000097:blood*; D002850:Chromatography, Gel; D005260:Female; D005502:Food; D005755:Gastrins / Q000096:biosynthesis* / Q000097:blood*; D005998:Glycine / Q000096:biosynthesis; D006801:Humans; D008297:Male; D010446:Peptide Fragments; D011498:Protein Precursors / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011863:Radioimmunoassay
D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C058638:tyrosyl-glycyl-tryptophyl-methionyl-aspartyl-phenylalanyl-glycine; C061391:cholecystokinin, Gly-; D002766:Cholecystokinin; D005998:Glycine