Rabbit NHE2 and NHE3 are two epithelial isoform Na+/H+ exchangers (NHE), the messages for which are found predominantly and entirely, respectively, in renal, intestinal, and gastric mucosa. The current studies used Western analysis and immunohistochemistry to identify and characterize the apical vs. basolateral membrane distribution of NHE2 and NHE3 in intestinal epithelial cells. Based on Western analysis, NHE2 and NHE3 both are present in brush-border but not basolateral membranes of small intestine. Both NHE2 and NHE3 are 85-kDa proteins. Consistent with Western analysis, NHE2 and NHE3 are immunolocalired to the brush-border but not basolateral membranes of villus epithelial cells, but not goblet cells, in human jejunum and ileum and in surface epithelial cells in the ascending and descending colon and rectum. In addition, NHE2 and NHE3 are present in small amounts in the crypt cell brush border of human jejunum, ileum, ascending and descending colon, and rectum. In rabbit jejunum, ileum, and ascending colon, NHE2 and NHE3 are present in the brush border of epithelial and not goblet cells, again much more in the villus (small intestine)/ surface cells (colon) than the crypt. NHE2 but not NHE3 is present in the brush border of rabbit descending colon surface cells and in small amounts in crypt cells. NHE2 and NHE3 are both human and rabbit small intestinal and colonic epithelial cell brush-border Na+/H+ exchanger isoforms that colocalize in all intestinal segments except rabbit descending colon, which lacks NHE3.

The murine gastrointestinal tract contains functional clock genes, which are molecular core components of the circadian clock. Daytime feeding in nocturnal rodents is a strong synchronizer of gastrointestinal clock genes. This synchronization occurs independently of the central clock. Gastric clock gene expression is not mediated through the vagal nerve. The presence of clock genes in the myenteric plexus and epithelial cells suggests a role for clock genes in circadian coordination of gastrointestinal functions such as motility, cell proliferation, and migration.

OBJECTIVES-Shift work has been associated with gastrointestinal symptoms such as abdominal pain, constipation, and diarrhea. These symptoms overlap with those reported by patients with functional bowel disorders. Because shift work will lead to misalignment between the endogenous circadian timing system and the external 24 h environment, we hypothesized that nurses participating in shift work will have a higher prevalence of functional bowel disorders when compared with nurses participating in day shifts.METHODS-Nurses engaged in patient care were invited to complete Rome III, irritable bowel syndrome-quality of life measure (IBS-QOL) and modified Sleep-50 questionnaires. Respondents were classified as working day, night, or rotating shifts. The prevalence of IBS, functional constipation, functional diarrhea, and individual gastrointestinal symptoms was determined.RESULTS-Data were available for 399 nurses (214 day shift, 110 night shift, and 75 rotating shift workers). Rotating shift nurses had a significantly higher prevalence of IBS compared to day shift nurses (48% vs. 31%, P < 0.01). Multivariable logistic regression correcting for age, gender, and sleep quality proved this association robust. IBS-QOL scores among groups were similar. Prevalence of functional constipation and functional diarrhea was similar between groups. Rotating shift nurses had a significantly higher prevalence of abdominal pain compared to day shift (81% vs. 54%, P < 0.0001) and night shift workers (61%, P = 0.003).CONCLUSIONS-Participation in shift work, especially rotating shift work, is associated with the development of IBS and abdominal pain that is independent of sleep quality. Circadian rhythm disturbances may have a function in the pathogenesis of IBS and abdominal pain.