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

Autor: Berni Canani R; Department of Pediatrics, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy. berni@unina.it, Secondo A, Passariello A, Buccigrossi V, Canzoniero LM, Ruotolo S, Puzone C, Porcaro F, Pensa M, Braucci A, Pedata M, Annunziato L, Guarino A
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2010 Jan 25; Vol. 626 (2-3), pp. 266-70. Date of Electronic Publication: 2009 Oct 09.
DOI: 10.1016/j.ejphar.2009.09.042
Abstrakt: Zn(2+) is effective in the treatment of acute diarrhea, but its mechanisms are not completely understood. We previously demonstrated that Zn(2+) 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 Zn(2+) inhibits intestinal ion secretion mediated by the Ca(2+) or nitric oxide pathways. To investigate ion transport we evaluated the effect of Zn(2+) (35 microM) on electrical parameters of human intestinal epithelial cell monolayers (Caco2 cells) mounted in Ussing chambers and exposed to ligands that selectively increased intracellular Ca(2+) (carbachol 10(-6)M) or nitric oxide (interferon-gamma 300 UI/ml) concentrations. We also measured intracellular Ca(2+) and nitric oxide concentrations. Zn(2+) significantly reduced ion secretion elicited by carbachol (-87%) or by interferon-gamma (-100%), and inhibited the increase of intracellular Ca(2+) and nitric oxide concentrations. These data indicate that Zn(2+) inhibits ion secretion elicited by Ca(2+) and nitric oxide by directly interacting with the enterocyte. They also suggest that Zn(2+) interferes with three of the four main intracellular pathways of intestinal ion secretion that are involved in acute diarrhea.
Databáze: MEDLINE
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