Abstract
The effect of endothelin-2 (ET-2) on neutrophil migration and intracellular calcium was studied. Depending on the concentration, ET-2 enhanced or inhibited neutrophil migration. At low concentrations ET-2 caused a chemotactic stimulation of migration, in contrast with endothelin-1 (ET-1) which caused a chemokinetic stimulation of migration. At higher concentrations ET-2 inhibited formyl-methionylleucyl-phenylalanine(fMLP)-activated migration. Both activation and inhibition by ET-2 were completely dependent on extracellular Ca2+. Unlike ET-1 which caused an increase in cytosolic free Ca2+ at a concentration which stimulated migration, ET-2 caused a measurable increase of cytosolic free Ca2+ at a concentration which did not stimulate migration. This strongly suggests that there is no correlation between maximal stimulation of cytoplasmic free calcium, and maximal stimulation of migration. Influx of extracellular Ca2+ was required for both activation of migration and change in cytosolic free Ca+, because no effect was observed in the absence of extracellular Ca+, and because blockers of Ca2+-influx inhibited ET-2-activated migration. The ETA-receptor antagonist cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) (BQ123), and the ETB-receptor antagonist [Cys11-Cys15]-endothelin-1(11–21) (IRL1038) antagonized the stimulatory effect of ET-2 on migration, and the inhibitory effect of high concentrations of ET-2 on fMLP-activated chemotaxis. This suggests that both the ETA-receptor and the ETB-receptor are involved in the stimulatory effect of low concentrations of ET-2, and in the inhibitory effect of high concentrations of ET-2.
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Elferink, J.G., de Koster, B.M. The effect of endothelin-2 (ET-2) on migration and changes in cytosolic free calcium of neutrophils. Naunyn-Schmiedeberg's Arch Pharmacol 353, 130–135 (1996). https://doi.org/10.1007/BF00168749
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DOI: https://doi.org/10.1007/BF00168749