Identification ofProgastrin inGastrinomas, Antrum, andDuodenumbya NovelRadioimmunoassay

Recent studies onthegenesequence encoding thehumanpyloric antral hormone, gastrin, indicate aprecursor of101residues. Wehavenowraised antibodies toasynthetic analogue corresponding to(Tyr)-human progastrin COOH-terminal pentapeptide. Theantibodies could beusedinradioimmunoassay tomeasurethis peptide, butthey didnotreact withcorresponding fragments ofprocholecystokinin, porcine progastrin, Orother human progastrin-derived peptides, notably heptadecapeptide gastrin (G17), and34-residue gastrin (G34). Radioimmunoassay ofhumanantral andduodenal extracts revealed amajor peakofactivity that corresponded tothenative COOH-terninal fragment ofprogastrin, andoccurred inapproximately equimolar amounts withCOOH-terminal G17immunoreactivity. Inaddition, there wasaminor peakofapparently higher molecular weight material. Insomegastrinomas thelatter material wasthepredominant immunoreactive form, anditoccurred inhigher molar concentrations thananyother formofgastrin. Digestion ofthis material withtrypsin liberated peptides that reacted with antibodies specific fortheNH2-terminus ofG34,andG17.Onthis basis the highmolecular weight component wasidentified asaformof gastrin that extended fromtheCOOH-termminus oftheprecursor toapoint atleast beyond theNHrterminus ofG34, andprobably included theentire progastrin sequence. Theresults suggest differences inposttranslational