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. (Inflamm Bowel Dis 2011;)
The stimulatory pathways controlling HCO 3 Ϫ secretion by the pancreatic ductal epithelium are well described. However, only a few data are available concerning inhibitory mechanisms, which may play an important role in the physiological control of the pancreas. The aim of this study was to investigate the cellular mechanism by which substance P (SP) inhibits pancreatic ductal HCO 3 Ϫ secretion. Small intra/interlobular ducts were isolated from the pancreas of guinea pigs. During overnight culture the ducts seal to form a closed sac. Transmembrane HCO 3 Ϫ fluxes were calculated from changes in intracellular pH (measured using the pH-sensitive dye BCECF) and the buffering capacity of the cells. We found that secretin can stimulate HCO 3 Ϫ secretion in guinea pig pancreatic ducts about fivefold and that this effect could be totally blocked by SP. The inhibitory effect of SP was relieved by spantide, an SP receptor antagonist. SP had no effect on the activity of basolateral Na ϩ -HCO 3 Ϫ cotransporters and Na ϩ /H ϩ exchangers. However, the peptide did inhibit a Cl Ϫ -dependent HCO 3
In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients.
It was shown for the first time that BK channels (i) are expressed at the apical membrane of guinea pig PDECs; (ii) have a crucial role in regulating HCO₃⁻ secretion and (iii) are also essential for the bile acid-induced hypersecretion and, therefore, underlie the response of the pancreas to this noxious agent.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.