Please use this identifier to cite or link to this item:
|Title:||Divergent roles for ferric ions in the biological activity of amidated and non-amidated gastrins.|
|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.|
|Citation:||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.|
|Internal ID Number:||15128280|
Receptor, Cholecystokinin B.metabolism
|Appears in Collections:||Journal articles|
Files in This Item:
There are no files associated with this item.
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.