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
Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes / BERNI CANANI, Roberto; Secondo, Agnese; Passariello, Annalisa; Buccigrossi, Vittoria; Canzoniero, Lm; Ruotolo, Serena; Puzone, C; Porcaro, Francesco; Pensa, M; Braucci, A; Pedata, M; Annunziato, Lucio; Guarino, Alfredo. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - STAMPA. - 626:2-3(2010), pp. 266-270. [10.1016/j.ejphar.2009.09.042]
Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes
BERNI CANANI, ROBERTO;SECONDO, AGNESE;PASSARIELLO, ANNALISA;BUCCIGROSSI, VITTORIA;RUOTOLO, SERENA;PORCARO, FRANCESCO;ANNUNZIATO, LUCIO;GUARINO, ALFREDO
2010
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 diarrheaFile | Dimensione | Formato | |
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