NHE2 and NHE3 are human and rabbit intestinal brush-border proteins

Abstract

Rabbit NHE2 and NHE3 are two epithelial isoform Na+/H+ exchangers (NHE), the messages for which are found predominantly and entirely, respectively, in renal, intestinal, and gastric mucosa. The current studies used Western analysis and immunohistochemistry to identify and characterize the apical vs. basolateral membrane distribution of NHE2 and NHE3 in intestinal epithelial cells. Based on Western analysis, NHE2 and NHE3 both are present in brush-border but not basolateral membranes of small intestine. Both NHE2 and NHE3 are 85-kDa proteins. Consistent with Western analysis, NHE2 and NHE3 are immunolocalired to the brush-border but not basolateral membranes of villus epithelial cells, but not goblet cells, in human jejunum and ileum and in surface epithelial cells in the ascending and descending colon and rectum. In addition, NHE2 and NHE3 are present in small amounts in the crypt cell brush border of human jejunum, ileum, ascending and descending colon, and rectum. In rabbit jejunum, ileum, and ascending colon, NHE2 and NHE3 are present in the brush border of epithelial and not goblet cells, again much more in the villus (small intestine)/ surface cells (colon) than the crypt. NHE2 but not NHE3 is present in the brush border of rabbit descending colon surface cells and in small amounts in crypt cells. NHE2 and NHE3 are both human and rabbit small intestinal and colonic epithelial cell brush-border Na+/H+ exchanger isoforms that colocalize in all intestinal segments except rabbit descending colon, which lacks NHE3.

Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

“…Although it does not play a role in the Na + absorption, it fulfils housekeeping functions, regulating cell volume and pH i [24]. In addition the presence of NHE2 and NHE3 on the apical membrane of colonic epithelial cells has been confirmed [20]. NHE3 knock out mice develope diarrhoea, which supports the idea that this might be the dominant NHE isoform, responsible for Na + uptake in the intestine [12,35,49].…”

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

“…It has been localized to several organs including the gut, skeletal muscle, kidney, brain, uterus, testis, heart and lung. In the gut, NHE2 is expressed in stomach, duodenum, ileum, jejunum, proximal and distal colon [67,139]. Within the kidney, NHE2 is expressed in the thick ascending limb (as well as the macula densa), distal convoluted tubules, connecting tubules and some thin ascending limbs [28].…”

“…Within the kidney, NHE2 is expressed in the thick ascending limb (as well as the macula densa), distal convoluted tubules, connecting tubules and some thin ascending limbs [28]. When expressed in epithelial cells it predominantly localizes to the apical membrane [67,28].…”

Tumor necrosis factor-α downregulates intestinal NHE8 expression by reducing basal promoter activity

“…NHE2-knockout mice display normal phenotype but have altered oxyntic mucosa of the gastric corpus and markedly reduced parietal and zymogenic cell number (7, 25). NHE3 protein is also expressed at the intestinal BBM (14,22). Lack of NHE3 expression in mice impairs acid-base balance and Na ϩ -fluid volume homeostasis (42).…”

“…Absence of NHE1 in mice exhibits decreased postnatal growth rate, ataxia, and seizures (5). NHE2 protein is localized to the brush-border membrane (BBM) in the intestinal epithelia (22). NHE2-knockout mice display normal phenotype but have altered oxyntic mucosa of the gastric corpus and markedly reduced parietal and zymogenic cell number (7,25).…”