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Title: Divergent roles for ferric ions in the biological activity of amidated and non-amidated gastrins.
Austin Authors: Pannequin, J;Tantiongco, J-P;Kovac, Suzana;Shulkes, Arthur;Baldwin, Graham S
Affiliation: University of Melbourne Department of Surgery, Austin Campus, A and RMC, Studley Road, Heidelberg, Victoria 3084, Australia
Issue Date: 1-May-2004
Publication information: The Journal of Endocrinology; 181(2): 315-25
Abstract: Amidated forms of the peptide hormone gastrin act via the cholecystokinin-2 receptor to stimulate gastric acid secretion, whereas non-amidated forms stimulate colonic mucosal proliferation via a novel, as yet uncharacterised, receptor. Nuclear magnetic resonance (NMR) and fluorescence spectroscopic studies have revealed that glycine-extended gastrin17 bound two ferric ions, and that ferric ion binding was essential for biological activity. We have therefore investigated the role of ferric ions in the biological activity of amidated gastrin17. As with glycine-extended gastrin17, fluorescence quenching experiments indicated that Glu7 Ala and Glu8,9 Ala mutants of amidated gastrin17 each bound only one ferric ion. The affinity of the mutant peptides for the cholecystokinin-2 receptor on transfected COS-7 cells or on Tlymphoblastoid Jurkat cells, and their potency in stimulation of proliferation in Jurkat cells and inositol phosphate production in transfected COS-7 cells, were similar to the values obtained for amidated gastrin17. In addition, the iron chelator desferrioxamine did not significantly inhibit either binding of amidated gastrin17 to the cholecystokinin-2 receptor, or stimulation of inositol phosphate production by amidated gastrin17 in transfected COS-7 cells. We conclude that, in contrast to glycine-extended gastrin17, binding of ferric ions is not essential for the biological activity of amidated gastrin17. Our results support the concept of distinct modes of action for amidated and non-amidated gastrins, and raise the possibility of developing selective antagonists of the actions of non-amidated and amidated gastrins.
Gov't Doc #: 15128280
Type: Journal Article
Subjects: Animals
COS Cells
Cell Division
Gastric Acid.secretion
Inositol Phosphates.metabolism
Jurkat Cells
Receptor, Cholecystokinin B.metabolism
Spectrometry, Fluorescence
Appears in Collections:Journal articles

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