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Am J Physiol Cell Physiol 268: C283-C296, 1995;
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AJP - Cell Physiology, Vol 268, Issue 2 C283-C296, Copyright © 1995 by American Physiological Society

ARTICLES

Hormonal regulation, pharmacology, and membrane sorting of vertebrate Na+/H+ exchanger isoforms

J. Noel and J. Pouyssegur
Centre de Biochimie Centre, Universite de Nice, Faculte des Sciences, France.

Since the cloning of the first member of the Na+/H+ exchanger (NHE) family, termed NHE1, four NHE isoforms have been cloned (NHE2, NHE3, NHE4, and the trout beta-NHE) and expressed in exchanger-deficient cell lines. All these isoforms exhibit significant identity to NHE1 and possess a similar hydropathy profile with two highly conserved transmembrane segments presumably involved in ion transport. These isoforms are allosterically activated by intracellular H+, regulate intracellular pH in a Na(+)-dependent manner, and are inhibited by amiloride and 5-amino derivatives with distinct Ki values. NHE1 is the amiloride-sensitive, growth factor-activatable, and ubiquitously expressed NHE known to regulate intracellular pH and cellular volume. NHE2, NHE3, and NHE4 are, however, restricted in their tissue distribution, suggesting roles in specialized functions of these epithelial tissues. In this review we present and discuss the most recent advances in the molecular and biochemical features, hormonal and growth factor activation, specific expression, and membrane sorting of the members of this NHE family.


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M. V. Cutaia, N. Parks, J. Centracchio, S. Rounds, K. P. Yip, and A. M. Sun
Effect of hypoxic exposure on Na+/H+ antiport activity, isoform expression, and localization in endothelial cells
Am J Physiol Lung Cell Mol Physiol, September 1, 1998; 275(3): L442 - L451.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
L. D. Shrode, B. S. Gan, S. J. A. D'Souza, J. Orlowski, and S. Grinstein
Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage
Am J Physiol Cell Physiol, August 1, 1998; 275(2): C431 - C439.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
R. C. Fitzgerald, M. B. Omary, and G. Triadafilopoulos
Altered sodium-hydrogen exchange activity is a mechanism for acid-induced hyperproliferation in Barrett's esophagus
Am J Physiol Gastrointest Liver Physiol, July 1, 1998; 275(1): G47 - G55.
[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. Cell Physiol.Home page
C. H. Joiner, M. Jiang, H. Fathallah, F. Giraud, and R. S. Franco
Deoxygenation of sickle red blood cells stimulates KCl cotransport without affecting Na+/H+ exchange
Am J Physiol Cell Physiol, June 1, 1998; 274(6): C1466 - C1475.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
I. Khan, F. M. Al-Awadi, and H. Abul
Colitis-Induced Changes in the Expression of the Na+/H+ Exchanger Isoform NHE-1
J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 869 - 875.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
S. D'Souza, A. Garcia-Cabado, F. Yu, K. Teter, G. Lukacs, K. Skorecki, H.-P. Moore, J. Orlowski, and S. Grinstein
The Epithelial Sodium-Hydrogen Antiporter Na+/H+ Exchanger 3 Accumulates and Is Functional in Recycling Endosomes
J. Biol. Chem., January 23, 1998; 273(4): 2035 - 2043.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
E. Feifel, M. Krall, J. P. Geibel, and W. Pfaller
Differential activities of H+ extrusion systems in MDCK cells due to extracellular osmolality and pH
Am J Physiol Renal Physiol, October 1, 1997; 273(4): F499 - F506.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
P. Isenring and B. Forbush III
Ion and Bumetanide Binding by the Na-K-Cl Cotransporter. IMPORTANCE OF TRANSMEMBRANE DOMAINS
J. Biol. Chem., September 26, 1997; 272(39): 24556 - 24562.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
E. Takahashi, J.-i. Abe, and B. C. Berk
Angiotensin II Stimulates p90rsk in Vascular Smooth Muscle Cells : A Potential Na+-H+ Exchanger Kinase
Circ. Res., August 19, 1997; 81(2): 268 - 273.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
R. Belusa, Z.-M. Wang, T. Matsubara, B. Sahlgren, I. Dulubova, A. C. Nairn, E. Ruoslahti, P. Greengard, and A. Aperia
Mutation of the Protein Kinase C Phosphorylation Site on Rat alpha 1 Na+,K+-ATPase Alters Regulation of Intracellular Na+ and pH and Influences Cell Shape and Adhesiveness
J. Biol. Chem., August 8, 1997; 272(32): 20179 - 20184.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
E. Krump, K. Nikitas, and S. Grinstein
Induction of Tyrosine Phosphorylation and Na+/H+ Exchanger Activation during Shrinkage of Human Neutrophils
J. Biol. Chem., July 11, 1997; 272(28): 17303 - 17311.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
M. P. Kelly, P. A. Quinn, J. E. Davies, and L. L. Ng
Activity and Expression of Na+-H+ Exchanger Isoforms 1 and 3 in Kidney Proximal Tubules of Hypertensive Rats
Circ. Res., June 19, 1997; 80(6): 853 - 860.
[Abstract] [Full Text]

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 HypertensionHome page
V. N. Phan, M. Kusuhara, P. A. Lucchesi, and B. C. Berk
A 90-kD Na+-H+ Exchanger Kinase Has Increased Activity in Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells
Hypertension, June 1, 1997; 29(6): 1265 - 1272.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
L. D. Shrode, E. A. Rubie, J. R. Woodgett, and S. Grinstein
Cytosolic Alkalinization Increases Stress-activated Protein Kinase/c-Jun NH2-terminal Kinase (SAPK/JNK) Activity and p38 Mitogen-activated Protein Kinase Activity by a Calcium-independent Mechanism
J. Biol. Chem., May 23, 1997; 272(21): 13653 - 13659.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. N. Garnovskaya, T. W. Gettys, T. van Biesen, V. Prpic, J. K. Chuprun, and J. R. Raymond
5-HT1A Receptor Activates Na+/H+ Exchange in CHO-K1 Cells through Gialpha 2 and Gialpha 3
J. Biol. Chem., March 21, 1997; 272(12): 7770 - 7776.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
V. Casavola, L. Guerra, S. J. Reshkin, K. A. Jacobson, and H. Murer
Polarization of Adenosine Effects on Intracellular pH in A6 Renal Epithelial Cells
Mol. Pharmacol., March 1, 1997; 51(3): 516 - 523.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. R. Ciriolo, A. T. Palamara, S. Incerpi, E. Lafavia, M. C. Bue, P. De Vito, E. Garaci, and G. Rotilio
Loss of GSH, Oxidative Stress, and Decrease of Intracellular pH as Sequential Steps in Viral Infection
J. Biol. Chem., January 31, 1997; 272(5): 2700 - 2708.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. Bianchini, G. L'Allemain, and J. Pouyssegur
The p42/p44 Mitogen-activated Protein Kinase Cascade Is Determinant in Mediating Activation of the Na+/H+ Exchanger (NHE1 Isoform) in Response to Growth Factors
J. Biol. Chem., January 3, 1997; 272(1): 271 - 279.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. A. Robertson, M. Woodside, J. K. Foskett, J. Orlowski, and S. Grinstein
Muscarinic Agonists Induce Phosphorylation-independent Activation of the NHE-1 Isoform of the Na+/H+ Antiporter in Salivary Acinar Cells
J. Biol. Chem., January 3, 1997; 272(1): 287 - 294.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
X. Lin, T. A. Voyno-Yasenetskaya, R. Hooley, C.-Y. Lin, J. Orlowski, and D. L. Barber
Galpha 12 Differentially Regulates Na+-H+ Exchanger Isoforms
J. Biol. Chem., September 13, 1996; 271(37): 22604 - 22610.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Orlowski and R. A. Kandasamy
Delineation of Transmembrane Domains of the Na+/H+ Exchanger That Confer Sensitivity to Pharmacological Antagonists
J. Biol. Chem., August 16, 1996; 271(33): 19922 - 19927.
[Abstract] [Full Text] [PDF]

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 Ann. Thorac. Surg.Home page
M. L. Myers and M. Karmazyn
Improved Cardiac Function After Prolonged Hypothermic Ischemia With the Na+/H+ Exchange Inhibitor HOE 694
Ann. Thorac. Surg., May 1, 1996; 61(5): 1400 - 1406.
[Abstract] [Full Text]

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 HypertensionHome page
W. Siffert and R. Dusing
Sodium-Proton Exchange and Primary Hypertension : An Update
Hypertension, October 1, 1995; 26(4): 649 - 655.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
K. Szaszi, K. Kurashima, A. Kapus, A. Paulsen, K. Kaibuchi, S. Grinstein, and J. Orlowski
RhoA and Rho Kinase Regulate the Epithelial Na+/H+ Exchanger NHE3. ROLE OF MYOSIN LIGHT CHAIN PHOSPHORYLATION
J. Biol. Chem., September 8, 2000; 275(37): 28599 - 28606.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
X. Luo, J. Y. Choi, S. B. H. Ko, A. Pushkin, I. Kurtz, W. Ahn, M. G. Lee, and S. Muallem
HCO3- Salvage Mechanisms in the Submandibular Gland Acinar and Duct Cells
J. Biol. Chem., March 23, 2001; 276(13): 9808 - 9816.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. V. Mukhin, T. Vlasova, A. A. Jaffa, G. Collinsworth, J. L. Bell, B. G. Tholanikunnel, T. Pettus, W. Fitzgibbon, D. W. Ploth, J. R. Raymond, et al.
Bradykinin B2 Receptors Activate Na+/H+ Exchange in mIMCD-3 Cells via Janus Kinase 2 and Ca2+/Calmodulin
J. Biol. Chem., May 11, 2001; 276(20): 17339 - 17346.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. Szaszi, K. Kurashima, K. Kaibuchi, S. Grinstein, and J. Orlowski
Role of the Cytoskeleton in Mediating cAMP-dependent Protein Kinase Inhibition of the Epithelial Na+/H+ Exchanger NHE3
J. Biol. Chem., October 26, 2001; 276(44): 40761 - 40768.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
L. Yang, P. K. K. Leong, J. O. Chen, N. Patel, S. F. Hamm-Alvarez, and A. A. McDonough
Acute hypertension provokes internalization of proximal tubule NHE3 without inhibition of transport activity
Am J Physiol Renal Physiol, April 1, 2002; 282(4): F730 - F740.
[Abstract] [Full Text] [PDF]


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