In birds, NHE2 is major brush-border Na⁺/H⁺ exchanger in colon and is increased by a low-NaCl diet

We previously reported that mammalian small intestinal and colonic brush borders (BBs) contained both epithelial Na⁺/H⁺ exchangers NHE2 and NHE3. We now show that, in the avian (chicken) colon, NHE2 is the major functional isoform under basal conditions and when stimulated by a low-NaCl diet. Hubbard chickens were maintained for 2 wk on a high- or low-NaCl diet. After the chickens were killed, the ileum and colon were removed, and BBs were prepared by Mg²⁺ precipitation and ²²Na and D-[¹⁴C]glucose uptake determined in the BB vesicles. NHE2 and NHE3 were separated by differential sensitivity to HOE-694 (NHE2 defined as Na⁺/H⁺ exchange inhibited by 50 μM HOE-694). Chickens on a low-Na⁺ diet have increased plasma aldosterone (10 vs. 207 pg/ml). On the high-NaCl diet, both NHE2 and NHE3 contributed to ileal and colonic apical Na⁺/H⁺ exchange, contributing equally in ileum, but NHE2 being the major component in colon (86%). Low-NaCl diet significantly increased ileal and colonic BB Na⁺/H⁺ exchange; the increase in BB Na⁺/H⁺ exchange in both ileum and colon was entirely due to an increase in NHE2 with no change in NHE3 activity. In contrast, low-NaCl diet decreased ileal and colonic Na⁺-dependent D-glucose uptake. Western analysis showed that low-Na⁺ diet increased the amount of NHE2 in the ileal and colonic BB and decreased the amount of ileal Na⁺-dependent glucose transporter SGLT1. Both NHE2 and NHE3 were present in the apical but not basolateral membranes (BLM) of ileal and colonic epithelial cells. In summary, 1) NHE2 and NHE8 are both present in the BB and not BLM of chicken ileum and colon; 2) NHE2 is the major physiological colonic BB Na⁺/H⁺ exchanger under basal conditions; 3) low-NaCl diet, which increases plasma aldosterone, increases ileal and colonic BB Na⁺/H⁺ exchange and decreases Na⁺-dependent D-glucose uptake; 4) the stimulation of colonic BB Na⁺/H⁺ exchange is due to increased activity and amount of NHE2; and 5) the inhibition of ileal D-glucose uptake is associated with a decrease in SGLT1 amount. NHE2 is the major chicken colonic BB Na⁺/H⁺ exchanger.