HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Stimulation of proliferation in the colorectal mucosa by gastrin precursors is blocked by desferrioxamine.

Abstract
Precursors of the peptide hormone gastrin stimulate proliferation in the colorectal mucosa and promote the development of colorectal carcinoma. Gastrins bind two ferric ions selectively and with high affinity, and the biological activity of glycine-extended gastrin (Ggly) in vitro is dependent on the presence of ferric ions. The aim of the present study was to determine whether or not iron is required for biological activity of progastrin and Ggly in vivo. Rats that had undergone a colostomy were infused with Ggly, and proliferation was measured in the defunctioned rectal mucosa. Proliferation was also measured in the colonic mucosa of hGAS and MTI-Ggly mice, which, by definition, overexpress progastrin and Ggly, respectively. The requirement for iron was assessed by thrice-weekly injection of the chelating agent desferrioxamine (DFO). The proliferation index in the defunctioned rectal mucosa was significantly increased in the Ggly-infused rats, and the increase was significantly reduced after treatment with DFO. Treatment with DFO significantly reduced the crypt height and proliferation index in the colonic mucosa of hGAS and MTI-Ggly mice but had no effect on the same variables in wild-type mice. These observations are consistent with the hypothesis that the biological activity of progastrin and Ggly in vivo is dependent on the presence of ferric ions and further suggest that chelating agents may block the stimulatory effects of gastrin precursors in the development of colorectal carcinoma.
AuthorsAudrey Ferrand, Shamilah Lachal, Gianni Bramante, Suzana Kovac, Arthur Shulkes, Graham S Baldwin
JournalAmerican journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 299 Issue 1 Pg. G220-7 (Jul 2010) ISSN: 1522-1547 [Electronic] United States
PMID20395538 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Gastrins
  • Protein Precursors
  • Siderophores
  • big gastrin
  • Iron
  • Deferoxamine
Topics
  • Animals
  • Cell Proliferation
  • Colon (drug effects, metabolism, pathology)
  • Colostomy
  • Deferoxamine (administration & dosage, pharmacology)
  • Female
  • Gastrins (administration & dosage, blood, genetics, metabolism)
  • Humans
  • Infusion Pumps, Implantable
  • Injections, Intraperitoneal
  • Intestinal Mucosa (drug effects, metabolism, pathology)
  • Iron (metabolism)
  • Male
  • Mice
  • Mice, Transgenic
  • Protein Precursors (administration & dosage, blood, genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Rectum (drug effects, metabolism, pathology)
  • Siderophores (administration & dosage, pharmacology)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: