[Co-existence and co-release of gastrin 34 N-terminal fragment with gastrin 17 in rat stomach].
Big gastrin comprising 34 amino acid residues (G34) consists of an N-terminal pentadecapeptide linked via two lysine residues to a C-terminal heptadecapeptide identical with little gastrin (G17). Both G17 and G34 have now been established as the principal active forms of gastrin. In this study, release of G34 N-terminal peptide fragment of methacholine and porcine gastrin releasing peptide (pGRP) stimulation in isolated rat stomach perfusion system was investigated by radioimmunoassay with use of an antiserum specific to the N-terminal portion of G34. G34 N-terminal immunoreactivity (IR-G34-N) was detected in rat stomach and proximal duodenum, and the highest concentration was found in extract of the antral mucosa. The concentration of IR-G34-N was constantly lower than that of IR-G17. By gel-filtration study, IR-G34-N in antral mucosa extract was attributed mostly to the G34 N-terminal pentadecapeptide-like component, and the concentration of G34 was about one tenth of G17. Methacholine 10(-8)-10(-3) M produced a biphasic dose-dependent release of IR-G34-N from the vascularly perfused isolated rat stomach. The maximal release was shown by 10(-5) M of methacholine. The release was concomitant with that of IR-G17 during methacholine stimulation. Stimulation of pGRP (14-27) (10(-7) M) produced a monophasic release of IR-G34-N from the vascularly perfused isolated rat stomach. The release was concomitant with that of G17 during the stimulation. The integrated IR-G34-N release was not stoichiometric with that of IR-G17, and IR-G34-N was constantly low. Gel-filtration of the perfusate from rat stomach revealed the presence of the G34 N-terminal pentadecapeptide-like component as a sole major component. The present results demonstrate that post-translational processing of the gastrin precursor in the rat antrum did not necessarily produce G34, which is further converted in the tissue to G17-related peptide(s) and that the G34 N-terminal fragment formed in the G34 conversion is stored and released concomitantly with G17-related peptide(s).
Akai
H
H
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D010455:Peptides; D010477:Perfusion / Q000379:methods; D011498:Protein Precursors / Q000378:metabolism*; D011706:Pyloric Antrum; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D005755:Gastrins; D008688:Methacholine Compounds; D010455:Peptides; D011498:Protein Precursors; D016210:Methacholine Chloride; C013706:big gastrin; C013550:gastrin 17; D019886:Gastrin-Releasing Peptide