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2015 ; 12
(8
): 446-57
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Secretory diarrhoea: mechanisms and emerging therapies
#MMPMID26122478
Thiagarajah JR
; Donowitz M
; Verkman AS
Nat Rev Gastroenterol Hepatol
2015[Aug]; 12
(8
): 446-57
PMID26122478
show ga
Diarrhoeal disease remains a major health burden worldwide. Secretory diarrhoeas
are caused by certain bacterial and viral infections, inflammatory processes,
drugs and genetic disorders. Fluid secretion across the intestinal epithelium in
secretory diarrhoeas involves multiple ion and solute transporters, as well as
activation of cyclic nucleotide and Ca(2+) signalling pathways. In many secretory
diarrhoeas, activation of Cl(-) channels in the apical membrane of enterocytes,
including the cystic fibrosis transmembrane conductance regulator and
Ca(2+)-activated Cl(-) channels, increases fluid secretion, while inhibition of
Na(+) transport reduces fluid absorption. Current treatment of diarrhoea includes
replacement of fluid and electrolyte losses using oral rehydration solutions, and
drugs targeting intestinal motility or fluid secretion. Therapeutics in the
development pipeline target intestinal ion channels and transporters, regulatory
proteins and cell surface receptors. This Review describes pathogenic mechanisms
of secretory diarrhoea, current and emerging therapeutics, and the challenges in
developing antidiarrhoeal therapeutics.
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