Formyl peptide stimulation of superoxide anion release from lung macrophages: sodium and potassium involvement.
We examined the role of the monovalent cations Na+ and K+ in the events encompassing the release of O-2 by alveolar macrophages after stimulation with formyl methionyl phenylalanine (FMP). This was accomplished by determining the effect of changing the extracellular [Na+] and/or [K+] on FMP-stimulated O-2 production; and measuring 22Na+, 42K+ and 86Rb+ influx and efflux and intracellular [K+] for control and FMP-stimulated alveolar macrophages. Stimulated O-2 production was relatively insensitive to changes in extracellular K+ or Na+ concentrations until the [Na+] was decreased below 35 mM. At 4 mM [Na+], the rate of O-2 production remained at 75% of the maximal rate observed at physiological concentrations of [Na+]. Both influx and efflux of 22Na+ were stimulated above control rates by FMP. The increased rates of fluxes lasted for a few minutes suggesting a transient increase in membrane permeability to Na+. Ouabain partially inhibited 22Na+ efflux but had no effect on O-2 release. The influx of 86Rb+ and 42K+ was not altered by the addition of FMP but was virtually abolished in the presence of 10 microM ouabain or 1 mM quinine. In the presence of extracellular calcium, FMP-stimulated a prolonged (greater than 20 minutes) increase in 86Rb+ or 42K+ efflux which was inhibitable by 1 mM quinine. In the absence of extracellular calcium, FMP stimulation of K+ efflux was greatly diminished and was not affected by quinine, although quinine still inhibited O-2 production under these conditions. It was also observed that there was a loss of intracellular K+ when cells were stimulated by FMP in the presence of Ca+2, but not in the absence of Ca+2. Taken together, these results suggest a minimal direct role, if any, for K+ in the events that lead to FMP-stimulated O-2 release by alveolar macrophages.
D000818:Animals; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D008264:Macrophages / Q000378:metabolism*; D008564:Membrane Potentials; D010100:Oxygen / Q000378:metabolism*; D011188:Potassium / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology; D011803:Quinine / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
D004151:Dipeptides; D013481:Superoxides; C017330:N-formylmethionylphenylalanine; D012964:Sodium; D011803:Quinine; D012413:Rubidium; D011188:Potassium; D010100:Oxygen