Abstracts
1998 Digestive Disease Week

#1295

SELECTIVE DECREASES IN LEVELS OF mRNA ENCODING A WATER CHANNEL (AQP3) IN ILEAL MUCOSA AFTER ILEOSTOMY. J. Purdy, R.R. Cima, M. A. Doble, M.J. Zinner, and D.I. Soybel. Dept. of Surgery, Brigham and Women's Hospital and West Roxbury V.A.M.C., Boston, MA.

Water channels (aquaporins) provide pathways for water permeation in a variety of epithelia. Aquaporin-3 (AQP3), has been localized to the small intestine but mechanisms that regulate its expression and function have not been explored. To determine whether the presence or absence of luminal contents may influence intestinal AQP3 expression, adult Sprague-Dawley rats underwent sham laparotomy (SHAM, n=5) or loop ileostomy (ILEO, n=5). Loop ileostomies were constructed proximal to the cecum, leaving 5 cm of ileum deprived of luminal content. Animals were fed ad libitum. Animals were sacrificed 8 days after procedures. Mucosa was harvested for isolation of total mRNA from jejunum, ileum proximal to the stoma, and ileum distal to the stoma. Northern analysis was used to measure mRNA levels for AQP3 and the Na+/K+ ATPase, a housekeeping transporter that regulates cellular levels of Na+ and K+. Results (mRNA measured by densitometry, normalized to GAPDH mRNA levels, and expressed as means ± SE, *p<0.05 compared to SHAM):

Through the 8 day period before sacrifice, weights were stable in all SHAM animals and declined by ~25% in all ILEO animals (p<0.001). At sacrifice, all regions of mucosa in SHAM animals were normal. In all ILEO animals, the jejunal and proximal ileal mucosa had not yet hypertrophied but the diverted distal ileum was already visibly atrophied. Little variation in Na/K mRNA levels was observed among different regions of the small intestine, in SHAM or ILEO animals. In ILEO animals, these levels were mildly elevated in the proximal ileal segment, consistent with increases in Na+ transport in this region that might be expected in the early response to loss of the colon. In contrast, levels of AQP3 mRNA were similar in jejunum and proximal ileal regions, but 2-fold higher in the distal ileum (P<0.0001). Ileostomy decreased AQP3 mRNA levels in this region markedly. These findings indicate regional variations in expression of water channels in mucosa of the small intestine. In addition, they suggest that AQP3 gene expression may be altered in response to luminal contents.

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