Lithium movements in resting and chemotactic factor-activated human neutrophils.
The ability of the chemotactic factor-activated Na+-H+ exchange system of human neutrophils to bind and transport other cations of the alkali metal series was investigated. After exposure of cells to the tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), the influx of Li+ was measured by flame photometry and correlated with changes in intracellular pH (pHi) derived from the equilibrium distribution of 5,5-dimethyloxazolidine-2,4-dione. In Na+-depleted cells, Li+ (Km approximately equal to 14 mM) could substitute effectively for Na+ (Km approximately equal to 23 mM) at the external translocation site of the carrier, though the maximal transport rate for Li+ (approximately 8 meq.l-1.min-1) was roughly half that for Na+ (approximately 15 meq.l-1.min-1). On the other hand, the carrier lacked appreciable affinity for K+, Rb+, and Cs+. The influx of Li+ from the external solution was accompanied by an equivalent counterefflux of H+ from the internal milieu. The H+ efflux thus induced led to an intracellular alkalinization of approximately 0.7 units, the pHi rising from approximately 7.20 to approximately 7.90. The influx of Li+, as well as the increase in pHi in 140 mM Li+ medium, was competitively inhibited by amiloride (Ki approximately equal to 9 microM). Extracellular H+ also behaved as a competitive inhibitor of Li+ with a Ki of approximately 30 nM (pK'a approximately 7.50). These studies indicate that the FMLP-activated alkali metal cation-H+ exchange mechanism of neutrophils shares a number of features in common with those of Na+-H+ exchangers in a variety of different cells.
Simchowitz
L
L
Department of Medicine, John Cochran Veterans Administration Medical Center, St. Louis, Missouri.
D000584:Amiloride / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002414:Cations, Monovalent; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000097:blood*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000097:blood
D002414:Cations, Monovalent; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000584:Amiloride; D008094:Lithium; D012964:Sodium