Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes.
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.
Berni Canani
Roberto
R
Department of Pediatrics, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy. berni@unina.it
Secondo
Agnese
A
Passariello
Annalisa
A
Buccigrossi
Vittoria
V
Canzoniero
Lorella Maria Teresa
LM
Ruotolo
Serena
S
Puzone
Cuono
C
Porcaro
Francesco
F
Pensa
Manuela
M
Braucci
Antonio
A
Pedata
Monica
M
Annunziato
Lucio
L
Guarino
Alfredo
A
D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007477:Ions / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D007477:Ions; D009569:Nitric Oxide; D015032:Zinc; D002118:Calcium