BACKGROUND: The absorption of water and ions (especially Na(+) and Cl(-)) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon. METHODS: In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na(+)/H(+) exchangers (NHE) 1-3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl(-)/HCO 3- exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques. RESULTS: Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na(+) absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl(-)/HCO 3- exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6-fold. CONCLUSIONS: These results open up new therapeutic targets in UC.
BACKGROUND: The absorption of water and ions (especially Na(+) and Cl(-)) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon. METHODS: In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na(+)/H(+) exchangers (NHE) 1-3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl(-)/HCO 3- exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques. RESULTS: Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na(+) absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl(-)/HCO 3- exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6-fold. CONCLUSIONS: These results open up new therapeutic targets in UC.
Authors: Claire B Larmonier; Daniel Laubitz; Faihza M Hill; Kareem W Shehab; Leszek Lipinski; Monica T Midura-Kiela; Rita-Marie T McFadden; Rajalakshmy Ramalingam; Kareem A Hassan; Marcin Golebiewski; David G Besselsen; Fayez K Ghishan; Pawel R Kiela Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-09-12 Impact factor: 4.052
Authors: Julie Tomas; Céline Mulet; Azadeh Saffarian; Jean-Baptiste Cavin; Robert Ducroc; Béatrice Regnault; Chek Kun Tan; Kalina Duszka; Rémy Burcelin; Walter Wahli; Philippe J Sansonetti; Thierry Pédron Journal: Proc Natl Acad Sci U S A Date: 2016-09-16 Impact factor: 11.205
Authors: C B Larmonier; D Laubitz; R D Thurston; A L Bucknam; F M Hill; M Midura-Kiela; R Ramalingam; P R Kiela; F K Ghishan Journal: Am J Physiol Gastrointest Liver Physiol Date: 2011-03-17 Impact factor: 4.052