title: Independence of dimethylamiloride-sensitive Li+ efflux pathways and Na+-Li+ countertransport in human erythrocytes.
abstract: The in vivo function of the erythrocyte Na+-Li+ countertransport (SLC) is unknown. Whether SLC may reflect an operational mode of the widespread Na+-H+ exchanger (NHE) or may otherwise be expression of an independent membrane transport, remains presently unclear. We explored the presence of 5-(N,N-dimethyl)-amiloride (DMA)-sensitive Li+ pathways in human erythrocytes where the activity of the Na+ pump, Na+-K+ cotransport and anion exchange were suitably inhibited. A total of 0.02 mM DMA had no effect on SLC as expected, but gave a significant inhibition of Li+ efflux into both Na+ and Na+-free media. This DMA-sensitive Li+ pathway, but not SLC, was significantly enhanced by hyperosmolar cell shrinkage, which is a characteristic feature of NHE. In conclusion, DMA-sensitive Li+ pathways, possibly mediated by NHE, are present in erythrocytes and coexist with the DMA-insensitive, SLC. This finding supports the notion that SLC is independent of amiloride-sensitive NHE.
authors.affiliation: Renal Pathophysiology Laboratory, Division of Medicine, Scientific Institute San Raffaele, University of Milan, Milan I-20132, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zerbini
authors.forename: R
authors.initials: R
authors.lastname: Mangili
authors.forename: G
authors.initials: G
authors.lastname: Pozza
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000838:Anions; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002794:Choline; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008094:Lithium / Q000378:metabolism*; D009997:Osmotic Pressure; D010042:Ouabain / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D000838:Anions; D017920:Antiporters; D017923:Sodium-Hydrogen Exchangers; C045885:sodium-lithium countertransporter; D002034:Bumetanide; C039465:5-dimethylamiloride; D010042:Ouabain; D000584:Amiloride; D008094:Lithium; D000254:Sodium-Potassium-Exchanging ATPase; D002794:Choline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010693:Phloretin