Expression of the human sodium/proton exchanger NHE-1 in Xenopus laevis oocytes enhances sodium/proton exchange activity and establishes sodium/lithium countertransport.
We investigated whether the human sodium/proton (Na+/H+) exchanger isoform 1 (NHE-1) can mediate sodium/lithium (Na+/Li+) countertransport. Using the Xenopus laevis oocyte expression system we determined amiloride-sensitive Li+ uptake, a measure of Na+/H+ exchange, in oocytes injected with water or NHE-1 cRNA. Amiloride-sensitive Li+ uptake was three- to tenfold enhanced over control in NHE-1 cRNA-injected cells and was selectively inhibited by 0.01 microM HOE 694 [i.e. (3-methylsulphonyl-4-piperidinobenzoyl) guanidine methanesulphonate]. The endogenously present Na+/H+ exchanger was insensitive to HOE 694. After acidification of oocytes from pH 7.7 to 6.8, amiloride-sensitive Li+ uptake was four- to tenfold higher in NHE-1 cRNA-injected cells than in controls. Li+ efflux from control oocytes was independent of extracellular Na+, indicating that these cells expressed no measurable Na+/Li+ countertransport activity. In NHE-1 cRNA-injected oocytes, Li+ efflux was distinctly enhanced by extracellular Na+ ions. This Na(+)-dependent Li+ efflux was inhibited by ethylisopropylamiloride, phloretin and by cytosolic acidification. The data show that expression of the NHE-1 in X. laevis oocytes induces the expression of Na+/Li+ countertransport. The data confirm that Na+/H+ exchange and Na+/Li+ countertransport are mediated by the same transport system.
Busch
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S
Max-Planck-Institut für Biophysik, Frankfurt, Germany.
Burckhardt
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BC
Siffert
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D000584:Amiloride / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D018075:RNA, Complementary / Q000235:genetics; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics*; D013450:Sulfones / Q000494:pharmacology; D014982:Xenopus laevis
D017920:Antiporters; D006146:Guanidines; D018075:RNA, Complementary; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C045885:sodium-lithium countertransporter; D000643:Ammonium Chloride; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; D000584:Amiloride; D009532:Nickel; D008094:Lithium; D012964:Sodium; D010693:Phloretin