Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa.
Water-coupled Na&sup+ absorption in the colon is mediated principally by Na+/H+ exchange (isoforms NHE2 and NHE3). To determine whether luminal ion composition 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 (154 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 following these infusions but were not as marked as the changes for NHE3. These findings suggest that (1) loss of luminal Na+ is not, in itself, a signal that regulates NHE expression and (2) infusion of any solute, including Na+ itself, provides a signal to downregulate expression of NHE3 in colon mucosa.
Doble
M A
MA
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Tola
V B
VB
Cima
R R
RR
Zinner
M J
MJ
Klein
M A
MA
Soybel
D I
DI
D000818:Animals; D015152:Blotting, Northern; D015536:Down-Regulation; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009994:Osmolar Concentration; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*
D020033:Protein Isoforms; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers