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Am J Physiol Gastrointest Liver Physiol 270: G29-G41, 1996;
0193-1857/96 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 1 29-G41, Copyright © 1996 by American Physiological Society

ARTICLES

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

W. A. Hoogerwerf, S. C. Tsao, O. Devuyst, S. A. Levine, C. H. Yun, J. W. Yip, M. E. Cohen, P. D. Wilson, A. J. Lazenby, C. M. Tse and M. Donowitz
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.

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.


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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Ikuma, M. Kashgarian, H. J. Binder, and V. M. Rajendran
Differential regulation of NHE isoforms by sodium depletion in proximal and distal segments of rat colon
Am J Physiol Gastrointest Liver Physiol, February 1, 1999; 276(2): G539 - G549.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Gonda, D. Maouyo, S. E. Rees, and M. H. Montrose
Regulation of intracellular pH gradients by identified Na/H exchanger isoforms and a short-chain fatty acid
Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G259 - G270.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Yang, W. Jiang, E. E. Furth, X. Wen, J. P. Katz, R. K. Sellon, D. G. Silberg, T. M. Antalis, C. W. Schweinfest, and G. D. Wu
Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea
Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1445 - G1453.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
J. F. Collins, P. R. Kiela, H. Xu, J. Zeng, and F. K. Ghishan
Increased NHE2 expression in rat intestinal epithelium during ontogeny is transcriptionally mediated
Am J Physiol Cell Physiol, October 1, 1998; 275(4): C1143 - C1150.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
J. H. Pizzonia, D. Biemesderfer, A. K. Abu-Alfa, M.-S. Wu, M. Exner, P. Isenring, P. Igarashi, and P. S. Aronson
Immunochemical characterization of Na+/H+ exchanger isoform NHE4
Am J Physiol Renal Physiol, October 1, 1998; 275(4): F510 - F517.
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 Am. J. Physiol. Renal Physiol.Home page
K.-P. Yip, C.-M. Tse, A. A. McDonough, and D. J. Marsh
Redistribution of Na+/H+ exchanger isoform NHE3 in proximal tubules induced by acute and chronic hypertension
Am J Physiol Renal Physiol, October 1, 1998; 275(4): F565 - F575.
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 Am. J. Physiol. Cell Physiol.Home page
R. L. McSwine, M. W. Musch, C. Bookstein, Y. Xie, M. Rao, and E. B. Chang
Regulation of apical membrane Na+/H+ exchangers NHE2 and NHE3 in intestinal epithelial cell line C2/bbe
Am J Physiol Cell Physiol, September 1, 1998; 275(3): C693 - C701.
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 Am. J. Physiol. Renal Physiol.Home page
R. Chambrey, D. G. Warnock, R.-A. Podevin, P. Bruneval, C. Mandet, M.-F. Belair, J. Bariety, and M. Paillard
Immunolocalization of the Na+/H+ exchanger isoform NHE2 in rat kidney
Am J Physiol Renal Physiol, September 1, 1998; 275(3): F379 - F386.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Donowitz, S. Khurana, C. M. Tse, and C. H. C. Yun
III. Asymmetry in plasma membrane signal transduction: lessons from brush-border Na+/H+ exchangers
Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G971 - G977.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Donowitz, C. De La Horra, M. L. Calonge, I. S. Wood, J. Dyer, S. M. Gribble, F. S. De Medina, C. M. Tse, S. P. Shirazi-Beechey, and A. A. Ilundain
In birds, NHE2 is major brush-border Na+/H+ exchanger in colon and is increased by a low-NaCl diet
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1998; 274(6): R1659 - R1669.
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 Am. J. Physiol. Cell Physiol.Home page
L. Wormmeester, F. S. De Medina, F. Kokke, C.-M. Tse, S. Khurana, J. Bowser, M. E. Cohen, and M. Donowitz
Quantitative contribution of NHE2 and NHE3 to rabbit ileal brush-border Na+/H+ exchange
Am J Physiol Cell Physiol, May 1, 1998; 274(5): C1261 - C1272.
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 Am. J. Physiol. Cell Physiol.Home page
J. H. Cho, M. W. Musch, C. M. Bookstein, R. L. McSwine, K. Rabenau, and E. B. Chang
Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon
Am J Physiol Cell Physiol, March 1, 1998; 274(3): C586 - C594.
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 Am. J. Physiol. Cell Physiol.Home page
J. F. Collins, H. Xu, P. R. Kiela, J. Zeng, and F. K. Ghishan
Functional and molecular characterization of NHE3 expression during ontogeny in rat jejunal epithelium
Am J Physiol Cell Physiol, December 1, 1997; 273(6): C1937 - C1946.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
C. Bookstein, Y. Xie, K. Rabenau, M. W. Musch, R. L. McSwine, M. C. Rao, and E. B. Chang
Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney
Am J Physiol Cell Physiol, November 1, 1997; 273(5): C1496 - C1505.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Orlowski and S. Grinstein
Na+/H+ Exchangers of Mammalian Cells
J. Biol. Chem., September 5, 1997; 272(36): 22373 - 22376.
[Full Text] [PDF]

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 J. Biol. Chem.Home page
J. W. Yip, W. H. Ko, G. Viberti, R. L. Huganir, M. Donowitz, and C.-M. Tse
Regulation of the Epithelial Brush Border Na+/H+ Exchanger Isoform 3 Stably Expressed in Fibroblasts by Fibroblast Growth Factor and Phorbol Esters Is Not through Changes in Phosphorylation of the Exchanger
J. Biol. Chem., July 18, 1997; 272(29): 18473 - 18480.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
C. H. C. Yun, S. Oh, M. Zizak, D. Steplock, S. Tsao, C.-M. Tse, E. J. Weinman, and M. Donowitz
cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein
PNAS, April 1, 1997; 94(7): 3010 - 3015.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. J. MacLeod and J. R. Hamilton
Activation of Na+/H+ Exchange Is Required for Regulatory Volume Decrease after Modest ``Physiological'' Volume Increases in Jejunal Villus Epithelial Cells
J. Biol. Chem., September 20, 1996; 271(38): 23138 - 23145.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
W. Lee-Kwon, D. C. Johns, B. Cha, M. Cavet, J. Park, P. Tsichlis, and M. Donowitz
Constitutively Active Phosphatidylinositol 3-Kinase and AKT Are Sufficient to Stimulate the Epithelial Na+/H+ Exchanger 3
J. Biol. Chem., August 10, 2001; 276(33): 31296 - 31304.
[Abstract] [Full Text] [PDF]


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