Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes.
BACKGROUND
Because zinc deficiency in malnourished children is associated with severe diarrhea, use of zinc supplementation has been proposed as an adjunct to oral rehydration. However, the effects of zinc on enterocyte ion transport are largely unknown. The objective of the present study was to investigate the effects of zinc on transepithelial ion transport under basal conditions and under conditions of enterotoxin-induced ion secretion.


METHODS
Ion transport was investigated by monitoring electrical parameters in human intestinal Caco-2 cells that were mounted in Ussing chambers and exposed to increasing concentrations of zinc, both in the absence and presence of either cholera toxin (CT) or Escherichia coli heat-stable enterotoxin (ST). Intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations were also determined.


RESULTS
The addition of zinc to the luminal or basolateral side of enterocytes induced a chloride-dependent, dose-related decrease in short-circuit current, indicating ion absorption. It also resulted in a substantial reduction in CT-induced ion secretion and in cAMP concentration. E. coli ST-induced ion secretion and cGMP concentration were not affected. Ion absorption peaked at 35 mu mol/L zinc, whereas excess zinc load induced active ion secretion.


CONCLUSIONS
By causing a decrease in cAMP concentration, zinc directly promotes ion absorption and substantially reduces CT-induced, but not E. coli ST-induced, ion secretion.
Canani
Roberto Berni
RB
Department of Pediatrics, University Federico II, Naples, Italy.
Cirillo
Pia
P
Buccigrossi
Vittoria
V
Ruotolo
Serena
S
Passariello
Annalisa
A
De Luca
Patrick
P
Porcaro
Francesco
F
De Marco
Giulio
G
Guarino
Alfredo
A
D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018938:Caco-2 Cells; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D020895:Enterocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli); D002772:Cholera Toxin; D000242:Cyclic AMP; D006152:Cyclic GMP; D015032:Zinc