title: Zinc sulphate attenuates chloride secretion in human colonic mucosae in vitro.
abstract: Zinc's usefulness in the treatment of diarrhoea is well established as an addition to oral rehydration. Mechanisms of action of zinc have been explored in intestinal epithelia from rodents and in cell lines. The aim was to examine how zinc alters ion transport and signal transduction in human colon in vitro. Voltage clamped colonic sheets obtained at the time of surgical resection were used to quantify ion transport responses to established secretagogues. Nystatin permeabilisation was used to study basolaterally-sited ion channels. Direct actions of zinc were determined using preparations of colonic crypts isolated from human mucosal sheets. Electrophysiological measurements revealed zinc to be an inhibitor of electrogenic ion transport stimulated by forskolin, PGE(2), histamine and carbachol in isolated human colonic epithelium. Basolateral addition of zinc sulphate had no direct effect on the epithelium. To further outline the mechanism of action, levels of secondary intracellular messengers (3', 5'-cyclic adenosine monophosphate; cAMP) were determined in isolated colonic crypts, and were found to be reduced by zinc sulphate. Finally, indirect evidence from nystatin-permeabilised mucosae further suggested that zinc inhibits basolateral K(+) channels, which are critical for transepithelial Cl(-) secretion linked to water flux. Anti-secretory, and therefore anti-diarrhoeal, actions of exogenous zinc are due, at least in part, to direct basolateral epithelial K(+) channel inhibition.
authors.affiliation: Institute for Clinical Outcomes Research and Education (ICORE), Department of Surgery, St Vincent's University Hospital, Dublin 4, Ireland.
authors.forename: Mekki
authors.initials: M
authors.lastname: Medani
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Bzik
authors.forename: Ailin
authors.initials: A
authors.lastname: Rogers
authors.forename: Danielle
authors.initials: D
authors.lastname: Collins
authors.forename: Rory
authors.initials: R
authors.lastname: Kennelly
authors.forename: Des C
authors.initials: DC
authors.lastname: Winter
authors.forename: David J
authors.initials: DJ
authors.lastname: Brayden
authors.forename: Alan W
authors.initials: AW
authors.lastname: Baird
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D019287:Zinc Sulfate