Abstract
In the mammalian small intestine, sodium is primarily absorbed by Na+/H+ exchange (NHE3) and Na‐glucose cotransport (SGLT1) in the brush border membrane (BBM) of villus cells. However, how enhanced cellular constitutive nitric oxide (cNO) may affect NHE3 and SGLT1 remains unclear. Both in vivo in rabbit intestinal villus cells and in vitro IEC‐18 cells, administration of NO donor, GSNAP, modestly increased cNO. GSNAP stimulated SGLT1 in villus and IEC‐18 cells. The mechanism of stimulation was secondary to an increase in the affinity of SGLT1 for glucose. The change in SGLT1 was not secondary to altered Na‐extruding capacity of the cell since Na+/K+‐ATPase was decreased by GSNAP treatment. In contrast, GSNAP inhibited NHE3 activity in villus cell BBM. The mechanism of NHE3 inhibition was secondary to reduced BBM transporter numbers. These studies demonstrated that the physiological increase in cNO uniquely regulates mammalian small intestinal NHE3 and SGLT1 to maintain Na homeostasis.
Highlights
The mammalian small intestine absorbs approximately 7.5 L of water every day, primarily mediated by the absorption of 650 mEq of sodium (Na)
When IEC18 cells were treated with 250 nmol/L GSNAP, it increased the intracellular constitutive nitric oxide (cNO) to modest levels as well (Fig. 1b)
This study demonstrates that a moderate increase in cNO stimulated SGLT1 in vivo in rabbit intestinal villus cells and in vitro in IEC-18 cells
Summary
The mammalian small intestine absorbs approximately 7.5 L of water every day, primarily mediated by the absorption of 650 mEq of sodium (Na). The two most important pathways of Na absorption in the small intestine are coupled electroneutral NaCl absorption and nutrient-dependent Na absorption. Coupled NaCl absorption occurs via the dual operation of Na+/H+ exchange (NHE3) and ClÀ/HCO3-exchange (DRA or PAT-1) located in the brush border membrane (BBM) of absorptive villus, but not secretory crypt cells. Na-glucose cotransport (SGLT1), located in the BBM of the villus cells, is the most abundant nutrient-dependent Na absorptive process in the mammalian small intestine (Hoogerwerf et al 1996; Sundaram et al 1997; Donowitz et al 2005; Coon et al 2007). SGLT1 is important for Na absorption, and for glucose absorption which is the most abundant nutrient in the diet (Wright et al 2006). The foundation of oral rehydration therapy is preserved SGLT1, which is the cornerstone of therapy for diarrheal diseases in developing countries
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