Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes

Roberto Berni Canani, Agnese Secondo, Annalisa Passariello, Vittoria Buccigrossi, Lorella Maria Teresa Canzoniero, Serena Ruotolo, Cuono Puzone, Francesco Porcaro, Manuela Pensa, Antonio Braucci, Monica Pedata, Lucio Annunziato, Alfredo Guarino

Research output: Contribution to journalArticle

Abstract

Zn2+ is effective in the treatment of acute diarrhea, but its mechanisms are not completely understood. We previously demonstrated that Zn2+ inhibits the secretory effect of cyclic adenosine monophosphate but not of cyclic guanosine monophosphate in human enterocytes. The aim of the present study was to investigate whether Zn2+ inhibits intestinal ion secretion mediated by the Ca2+ or nitric oxide pathways. To investigate ion transport we evaluated the effect of Zn2+ (35 μM) on electrical parameters of human intestinal epithelial cell monolayers (Caco2 cells) mounted in Ussing chambers and exposed to ligands that selectively increased intracellular Ca2+ (carbachol 10- 6 M) or nitric oxide (interferon-γ 300 UI/ml) concentrations. We also measured intracellular Ca2+ and nitric oxide concentrations. Zn2+ significantly reduced ion secretion elicited by carbachol (- 87%) or by interferon-γ (- 100%), and inhibited the increase of intracellular Ca2+ and nitric oxide concentrations. These data indicate that Zn2+ inhibits ion secretion elicited by Ca2+ and nitric oxide by directly interacting with the enterocyte. They also suggest that Zn2+ interferes with three of the four main intracellular pathways of intestinal ion secretion that are involved in acute diarrhea.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalEuropean Journal of Pharmacology
Volume626
Issue number2-3
DOIs
Publication statusPublished - Jan 25 2010

Keywords

  • Acute gastroenteritis
  • Intestinal ion transport
  • Intestinal pathogens

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Berni Canani, R., Secondo, A., Passariello, A., Buccigrossi, V., Canzoniero, L. M. T., Ruotolo, S., Puzone, C., Porcaro, F., Pensa, M., Braucci, A., Pedata, M., Annunziato, L., & Guarino, A. (2010). Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes. European Journal of Pharmacology, 626(2-3), 266-270. https://doi.org/10.1016/j.ejphar.2009.09.042