Abstracts
1997 Digestive Disease Week

Selective long-term increase in gastric mucosal nRNA encoding basal Na-K-Cl cotransporter following ileostomy in the rat.

H Hallonquist, RR Cima, ME Klingensmith, E Delpire, MJ Zinner, DI Soybel. Department of Surgery, Brigham and Women's Hospital, and Department of Critical Care Medicine, Children's Hospital, Boston, MA.

Previous studies have indicated that gastric mucosa undergoes hypertrophy in response to massive enterectomy or to creation of a permanent enterostomy. While resection-induced hypertrophy is associated with increases in levels of circulating gastrin and gastric acid secretion, diversion-induced hypertrophy is not. We hypothesized that diversion of intestinal contents leads to proliferation of the mucussecreting gastric surface epithelium but not of the acid-secreting gastric glands. To evaluate this hypothesis, adult Sprague-Dawley rats underwent sham laparotomy (n=5) or loop ileostomy (n=5). Animals were fed ad libitum. Weights were monitored for 3-4 weeks and following stabilization, animals were sacrificed. At the time of sacrifice, gastric mucosa was scraped and prepared for Northern analysis of levels of mRNAs encoding for: 1) omeprazole-sensitive H/K ATPase (H/K), a transporter localized to the apical membrane of the parietal cells; 2) bumetanide-sensitive Na-K-Cl cotransporter (Na-K-Cl), a transporter found in basal membranes of the parietal cells, but also abundant in the mucus-secreting surface epithelium; and 3) ouabain-sensitive Na/K ATPase (Na/K), a transporter found in all gastric epithelial cells. GAPDH mRNA levels were measured to control for equivalence of gel loading. Results were as follows (mRNA measured by densitometry and expressed as means±SE, *p<0.05 compared to sham-operated animals).

                       H/K           Na-K-Cl        Na/K
 SHAM                 100±15         100±14        100±15
 ILEOSTOMY            123±17         245±19*       114±14

Gastric mucosa from animals undergoing ileostomy was visibly hypertrophied compared to that from sham-operated animals. Levels of Na/K mRNA were not increased, indicating that mucosal hypertrophy was not associated with non-specific increases in expression of epithelial ion transport processes. Levels of H/K mRNA in tissues from ileostomy rats were not significantly different from those in sham-operated animals, indicating that mucosal hypertrophy was not associated with increases in expression of transporters not directly involved in H⁺ secretion. In contrast, levels of Na-K-Cl mRNA were increased an average 145% over those of the sham group, indicating that ileostomy selectively increases transcription of ion transporters that are involved in surface cell secretion. These findings suggest that, in the long term, creation of an ileostomy enhances secretory functions of the surface epithelium but not the acid-secreting glands. Further studies are required to understand the neurohumoral stimuli that mediate this selective trophic response.