PMID- 8717152 OWN - NLM STAT- MEDLINE DCOM- 19961022 LR - 20190726 IS - 0028-1298 (Print) IS - 0028-1298 (Linking) VI - 353 IP - 2 DP - 1996 Jan TI - The effect of endothelin-2 (ET-2) on migration and changes in cytosolic free calcium of neutrophils. PG - 130-5 AB - 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-methionyl-leucyl-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 Ca2+, because no effect was observed in the absence of extracellular Ca2+, and because blockers of Ca(2+)-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. FAU - Elferink, J G AU - Elferink JG AD - Department of Medical Biochemistry, University of Leiden, Netherlands. FAU - de Koster, B M AU - de Koster BM LA - eng PT - Journal Article PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Endothelins) RN - CJ0O37KU29 (Verapamil) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Chemotaxis/*drug effects MH - Dose-Response Relationship, Drug MH - Endothelins/*pharmacology MH - Neutrophils/*drug effects MH - Rabbits MH - Verapamil/pharmacology EDAT- 1996/01/01 00:00 MHDA- 1996/01/01 00:01 CRDT- 1996/01/01 00:00 PHST- 1996/01/01 00:00 [pubmed] PHST- 1996/01/01 00:01 [medline] PHST- 1996/01/01 00:00 [entrez] AID - 10.1007/BF00168749 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 1996 Jan;353(2):130-5. doi: 10.1007/BF00168749.