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

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 mu M) 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-gamma 300Ul/ml) concentrations. We also measured intracellular Ca2+ and nitric oxide concentrations. Zn2+ significantly reduced ion secretion elicited by carbachol (-87%) or by interferon-gamma (-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. (C) 2009 Elsevier BY. All rights reserved.