Molecular bases of impaired water and ion movements in inflammatory bowel diseases.
The intestine is dedicated to the absorption of water and nutrients. Fine tuning of this process is necessary to maintain an adequate balance and inflammation disrupts the equilibrium. This review summarizes the current evidence in this field. Classical mechanisms proposed include alteration of epithelial integrity, augmented secretion, and reduced absorption. In addition, intestinal inflammation is associated with defects in epithelial barrier function. However, our understanding of the phenomenon has been complicated by the fact that ionic secretion is in fact diminished in vivo, even after inflammation has subsided. Inhibited ionic secretion can be reversed partially or totally in vitro by maneuvers such as blockade of inducible nitric oxide synthase or removal of the submucosal layer. Disturbances in ionic absorption are less well characterized but clearly involve both electroneutral and electrogenic Na(+) absorption. Altered ionic transport is associated with changes in the expression and function of the transporters, including the Na(+)/K(+) ATPase, the sodium/potassium/chloride cotransporter 1 (NKCC1), the sodium/hydrogen exchanger 3 (NHE3), and the epithelial sodium channel (ENaC), as well as to the modulation of intracellular signaling. Further investigation is needed in this area in order to provide an integrated paradigm of ionic transport in the inflamed intestine. In particular, we do not know exactly how diarrhea ensues in inflammation and, consequently, we do not have specific pharmacological tools to combat this condition effectively and without side effects. Moreover, whether transport disturbances are reversible independently of inflammatory control is unknown.
Martínez-Augustin
Olga
O
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain.
Romero-Calvo
Isabel
I
Suárez
María Dolores
MD
Zarzuelo
Antonio
A
de Medina
Fermín Sánchez
FS
D000818:Animals; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D017136:Ion Transport; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance
D014867:Water