HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 4, 2453-2460, January 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/4/2453    most recent M309806200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pannequin, J. Articles by Baldwin, G. S. Search for Related Content PubMed PubMed Citation Articles by Pannequin, J. Articles by Baldwin, G. S. Social Bookmarking                      What's this?

A Novel Effect of Bismuth Ions

SELECTIVE INHIBITION OF THE BIOLOGICAL ACTIVITY OF GLYCINE-EXTENDED GASTRIN^*

Julie Pannequin, Suzana Kovac, John-Paul Tantiongco, Raymond S. Norton, Arthur Shulkes, Kevin J. Barnham¶, and Graham S. Baldwin||

From the Department of Surgery, University of Melbourne, Austin Campus, ARMC, Heidelberg, Victoria 3084, Australia, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Victoria 3050, Australia, and the ^¶Department of Pathology, The University of Melbourne, and The Mental Health Research Institute of Victoria, Parkville, Victoria 3010, Australia

Although bismuth salts have been used for over two centuries for the treatment of various gastrointestinal disorders, the mechanism of their therapeutic action remains controversial. Because gastrins bind two trivalent ferric ions with high affinity, and because ferric ions are essential for the biological activity of glycine-extended gastrin 17, we have investigated the hypothesis that trivalent bismuth ions influence the biological activity of gastrins. Binding of bismuth ions to gastrins was measured by fluorescence quenching and NMR spectroscopy. The effects of bismuth ions on gastrin-stimulated biological activities were measured in inositol phosphate, cell proliferation, and cell migration assays. Fluorescence quenching experiments indicated that both glycine-extended and amidated gastrin 17 bound two bismuth ions. The NMR spectral changes observed on addition of bismuth ions revealed that Glu-7 acted as a ligand at the first bismuth ion binding site. In the presence of bismuth ions the ability of glycine-extended gastrin 17 to stimulate inositol phosphate production, cell proliferation, and cell migration was markedly reduced. In contrast, bismuth ions had little effect on the affinity of the CCK-2 receptor for amidated gastrin 17, or on the stimulation of inositol phosphate production by amidated gastrin 17. We conclude that bismuth ions may act, at least in part, by blocking the effects of glycine-extended gastrin 17 on cell proliferation and cell migration in the gastrointestinal tract. This is the first report of a specific inhibitory effect of bismuth ions on the action of a gastrointestinal hormone.

Received for publication, September 4, 2003

^* This work was supported by Australian Research Council Grant A00103736 (to G. S. B. and R. S. N.), National Health and Medical Research Council of Australia Grants 980625 (to G. S. B.), 208926 (to G. S. B.), and 114123 (to A. S.), National Institutes of Health Grant GM65926-01 (to G. S. B., R. S. N., and A. S.), and the Austin Hospital Medical Research Foundation (to G. S. B. and A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Surgery, Austin Campus, A&RMC, Studley Road, Heidelberg, Victoria 3084, Australia. Tel.: 613-9496-5592; Fax: 613-9458-1650; E-mail: grahamsb{at}unimelb.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?