Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa

Water-coupled Na+ absorption in the colon is mediated principally by Na+/H exchange (isoforms NHE2 and NHE3). To determine whether luminal ion compos ition or osmolarity influences NHE expression in colon mucosa, two groups ( n = 6 in each) of adult male Sprague-Dawley rats underwent sham laparotomy or loop ileostomy. In these studies, diversion did not markedly alter mRNA levels for NHE2, NHE3, or Na+/K+, at 8 or 21 days, indicating that loss of luminal volume does not alter NHE gene expression. To evaluate the effects of specific luminal components, we infused equal volumes of half-normal (15 4 mOsm) or iso-osmolar (308 mOsm) solutions of saline and mannitol into the diverted colon. All solutions elicited significant (45% to 60%; P < 0.05) decreases in mRNA levels for NHE3, with iso-osmolar mannitol eliciting the greatest changes. Decreases in NHE2 and Na+/K+ mRNA levels were observed fo llowing these infusions but were not as marked as the changes for NHE3. The se findings suggest that (1) loss of luminal Naf is not, in itself, a signa l that regulates NHE expression and (2) infusion of any solute, including N a+ itself, provides a signal to downregulate expression of NHE3 in colon mu cosa.