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Slc9a2  -  solute carrier family 9, subfamily A (NHE2...

Rattus norvegicus

Synonyms: H7, NHE-2, Na(+)/H(+) exchanger 2, Nhe2, Sodium/hydrogen exchanger 2, ...
 
 
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Disease relevance of Slc9a2

  • This study demonstrated a direct effect of metabolic acidosis on NHE2 and NHE3 activity, expression, and gene transcription [1].
  • Although none of the NHE mRNA levels was altered in the transition from euthyroid to hypothyroid states, both NHE2 and NHE3 mRNA levels increased 1.5-fold in the transition from hypo- to hyperthyroidism [2].
  • In addition, in the isolated perfused rat liver, we studied the prophylactic effect of the PKc inhibitor H7 on phalloidin-induced cholestasis [3].
 

High impact information on Slc9a2

  • The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO(3)(-) absorption [4].
  • Similarly, inhibitors of protein kinase C (H-7 and sphingosine) diminished or abolished the rise in pHi after endothelin superfusion while causing a decline in its inotropic effect comparable with that observed with amiloride [5].
  • To clarify the signal transduction pathway from tyrosine kinase to the Na+/H+ exchanger, we examined the effects of inhibitors of other kinases (H-7, H-8, and W-7) on the HGF-induced pHi elevation and found that only W-7 blocked it [6].
  • These results indicated that the rat NHE-2 cDNA encodes a functional Na/H exchanger isoform with distinct properties compared to rat NHE-1 and -3 [7].
  • Biochemical analyses showed that the extracellular Na+ dependence of NHE-2 followed simple, saturating Michaelis-Menten kinetics with an apparent affinity constant for Na+ (KNa) of 50 mM [7].
 

Biological context of Slc9a2

  • Epidermal growth factor regulation of rat NHE2 gene expression [8].
  • Additionally, NHE2 promoter reporter gene assays in transiently transfected RIE cells showed an almost twofold increase in promoter activity after EGF treatment [8].
  • In acinar cells superfused with a physiological salt solution (145 mM Na+), Na+/H+ exchanger activity was inhibited by low concentrations of the amiloride derivative ethylisopropyl amiloride (EIPA; IC50 = 0.014 +/- 0.005 microM), suggesting the expression of amiloride-sensitive isoforms NHE1 and/or NHE2 [9].
  • We demonstrate for the first time that a mammalian Na(+)/H+ exchanger transports alkali metal cations in yeast in the opposite direction than in mammalian cells, and that the substrate specificity of the rat NHE2 exchanger is limited only to potassium cations upon expression in yeast cells [10].
  • We have recently cloned a novel Na+/H+ exchanger (NHE-2) from rat small intestinal cDNA library [11].
 

Anatomical context of Slc9a2

  • These results are consistent with the conclusion that NHE2 rather than NHE3 is the predominant isoform responsible for apical membrane Na(+)/H(+) exchange in the distal convoluted tubule, whereas NHE3 is the predominant apical isoform in the proximal tubule and possibly also in the loop of Henle [12].
  • A-II treatment did not alter brush border NHE2 protein abundance in the renal proximal tubules [13].
  • In ileal epithelial cells incubated in HCO/Ringer or HEPES/Ringer solution, the number of subapical vesicles, the relative quantity of apical membrane NHE isoforms 2 and 3 (NHE2 and NHE3, respectively), and apical membrane fluorescence under the confocal microscope were not affected by pH values between 7.1 and 7 [14].
  • The effect of specific inhibitors of NHE-2 and NHE-3 isoforms (50 microM HOE 694 and 2 microM S3226, respectively) on unidirectional 22Na transepithelial fluxes performed across isolated mucosa from rat distal colon under voltage-clamp conditions was examined [15].
  • Conclusion: PC-Cl3 cells express a functional Na/H exchange activity and different isoforms (NHE1, NHE2 and NHE3) are expressed in the plasma membrane [16].
 

Associations of Slc9a2 with chemical compounds

  • Effect of angiotensin-II on renal Na+/H+ exchanger-NHE3 and NHE2 [13].
  • The effects of mucosal 5-(N,N-dimethyl)-amiloride (DMA), which inhibits NHE2 and/or NHE3, and wortmannin, which inhibits phosphatidylinositol 3-kinase, on CO2-stimulated Na+ absorption were measured in the Ussing chamber [17].
  • It is suggested that NHE1 may provide "housekeeping" functions in both epithelia, whereas NHE2 in the cauda epididymidis and NHE3 in the efferent duct may be involved in Na+ reabsorption and regulation of pH of the luminal fluid [18].
  • Dibutyryl cAMP does not inhibit butyrate-stimulated Na absorption as a result of its differential effects on NHE-2 and NHE-3 isoforms [15].
  • EGF increased functional NHE2 activity and mRNA abundance in cultured RIE cells, and this stimulation could be blocked by actinomycin D (a transcriptional inhibitor) [8].
 

Analytical, diagnostic and therapeutic context of Slc9a2

  • In this study we evaluated the effects of ileostomy on messenger RNA levels that encode different Na(+)/H(+) exchanger isoforms (NHE-2 and NHE-3) [19].
  • In situ hybridization of NHE2 mRNA localized the message to the renal inner cortex and outer medullary regions and suggested higher mRNA levels in suckling animals as compared to adults [20].
  • In situ hybridization of 2- and 6-wk-old rat intestine with NHE2-specific probes confirmed Northern blot observations [21].
  • Western blots with NHE2 antiserum showed that the intensity of a specific 90-kDa band was lowest in 2-wk-old animals and four- to sixfold higher in 3- and 6-wk-old and adult animals [21].
  • Molecular cloning and expression have previously defined three members of the Na+/H+ exchanger (NHE) gene family NHE1 and NHE2 are sensitive to inhibition by amiloride and its 5'-amino alkyl-substituted analogues, whereas NHE3 is quite resistant to amiloride inhibition [22].

References

  1. Metabolic acidosis in rats increases intestinal NHE2 and NHE3 expression and function. Lucioni, A., Womack, C., Musch, M.W., Rocha, F.L., Bookstein, C., Chang, E.B. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  2. Renal Na+/H+ exchanger isoforms and their regulation by thyroid hormone. Azuma, K.K., Balkovetz, D.F., Magyar, C.E., Lescale-Matys, L., Zhang, Y., Chambrey, R., Warnock, D.G., McDonough, A.A. Am. J. Physiol. (1996) [Pubmed]
  3. Role of glutathione and oxidative stress in phalloidin-induced cholestasis. Bouchard, G., Yousef, I.M., Barriault, C., Tuchweber, B. J. Hepatol. (2000) [Pubmed]
  4. Hyposmolality stimulates apical membrane Na(+)/H(+) exchange and HCO(3)(-) absorption in renal thick ascending limb. Watts, B.A., Good, D.W. J. Clin. Invest. (1999) [Pubmed]
  5. Endothelin and increased contractility in adult rat ventricular myocytes. Role of intracellular alkalosis induced by activation of the protein kinase C-dependent Na(+)-H+ exchanger. Krämer, B.K., Smith, T.W., Kelly, R.A. Circ. Res. (1991) [Pubmed]
  6. Activation of Na+/H+ exchanger by hepatocyte growth factor in hepatocytes. Kaneko, A., Hayashi, N., Tanaka, Y., Horimoto, M., Ito, T., Sasaki, Y., Fusamoto, H., Kamada, T. Hepatology (1995) [Pubmed]
  7. Functional properties of the rat Na/H exchanger NHE-2 isoform expressed in Na/H exchanger-deficient Chinese hamster ovary cells. Yu, F.H., Shull, G.E., Orlowski, J. J. Biol. Chem. (1993) [Pubmed]
  8. Epidermal growth factor regulation of rat NHE2 gene expression. Xu, H., Collins, J.F., Bai, L., Kiela, P.R., Lynch, R.M., Ghishan, F.K. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  9. Expression of multiple Na+/H+ exchanger isoforms in rat parotid acinar and ductal cells. Park, K., Olschowka, J.A., Richardson, L.A., Bookstein, C., Chang, E.B., Melvin, J.E. Am. J. Physiol. (1999) [Pubmed]
  10. Mammalian NHE2 Na(+)/H+ exchanger mediates efflux of potassium upon heterologous expression in yeast. Flegelova, H., Sychrova, H. FEBS Lett. (2005) [Pubmed]
  11. Expression of a novel sodium-hydrogen exchanger in the gastrointestinal tract and kidney. Ghishan, F.K., Knobel, S., Barnard, J.A., Breyer, M. J. Membr. Biol. (1995) [Pubmed]
  12. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. Wang, T., Hropot, M., Aronson, P.S., Giebisch, G. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  13. Effect of angiotensin-II on renal Na+/H+ exchanger-NHE3 and NHE2. Dixit, M.P., Xu, L., Xu, H., Bai, L., Collins, J.F., Ghishan, F.K. Biochim. Biophys. Acta (2004) [Pubmed]
  14. Acid-base effects on intestinal Na(+) absorption and vesicular trafficking. Charney, A.N., Egnor, R.W., Alexander-Chacko, J., Cassai, N., Sidhu, G.S. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  15. Apical NHE isoforms differentially regulate butyrate-stimulated Na absorption in rat distal colon. Krishnan, S., Rajendran, V.M., Binder, H.J. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  16. Characterization of Na(+)/H(+) antiporter activity in PC-Cl3 thyroid cells. Vilella, S., Schiavone, R., Zilli, L., Marsigliante, S., Storelli, C. Cell. Physiol. Biochem. (2003) [Pubmed]
  17. Carbon dioxide affects rat colonic Na+ absorption by modulating vesicular traffic. Charney, A.N., Egnor, R.W., Cassai, N., Sidhu, G.S. Gastroenterology (2002) [Pubmed]
  18. Expression of multiple Na+/H+ exchanger isoforms in cultured epithelial cells from rat efferent duct and cauda epididymidis. Leung, G.P., Tse, C.M., Chew, S.B., Wong, P.Y. Biol. Reprod. (2001) [Pubmed]
  19. Luminal regulation of Na(+)/H(+) exchanger gene expression in rat ileal mucosa. Doble, M.A., Tola, V.B., Chamberlain, S.A., Cima, R.R., Van Hoek, A., Soybel, D.I. J. Gastrointest. Surg. (2002) [Pubmed]
  20. Expression of rat, renal NHE2 and NHE3 during postnatal development. Collins, J.F., Kiela, P.R., Xu, H., Ghishan, F.K. Biochim. Biophys. Acta (2000) [Pubmed]
  21. Increased NHE2 expression in rat intestinal epithelium during ontogeny is transcriptionally mediated. Collins, J.F., Kiela, P.R., Xu, H., Zeng, J., Ghishan, F.K. Am. J. Physiol. (1998) [Pubmed]
  22. Heterologous expression of rat NHE4: a highly amiloride-resistant Na+/H+ exchanger isoform. Chambrey, R., Achard, J.M., Warnock, D.G. Am. J. Physiol. (1997) [Pubmed]
 
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