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The stimulation of human neutrophil migration by angiotensin II: its dependence on Ca 2+ and the involvement of cyclic GMP
Author(s) -
Elferink Jan G. R.,
Koster Ben M.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701167
Subject(s) - angiotensin ii , pertussis toxin , stimulation , medicine , endocrinology , renin–angiotensin system , chemotaxis , calcium , extracellular , angiotensin receptor , chemistry , biology , receptor , biochemistry , g protein , blood pressure
Angiotensin II had a bimodal effect on human neutrophil migration. Low concentrations of angiotensin II stimulated random migration. At a concentration of 10 −10 M it caused a maximal increase of migration; migration increased from 47.2±2.1 μm in the absence of angiotensin II, to 73.1±2.2 μm with 10 −10 M angiotensin II present in the lower compartment of the Boyden chamber ( n =5, P <0.001). Stimulation of migration by angiotensin II was partly chemotactic and partly chemokinetic. Angiotensin II concentrations of 10 −8 M and higher inhibited chemotactic peptide‐stimulated chemotaxis. The stimulant effect of angiotensin II on migration was completely dependent on extracellular Ca 2+ . In the presence of 1 m M Ca 2+ , angiotensin II stimulated migration to 76.1±1.7 μm, while migration in the absence of Ca 2+ was 42.2±1.9 μm ( n =4, P <0.001). Different types of calcium channel blockers either moderately or strongly inhibited angiotensin II‐activated migration. Stimulation of migration by angiotensin II in intact cells required higher concentrations of Ca 2+ than in electroporated cells. This supports the view that there is an influx of Ca 2+ through the plasma membrane, and a requirement of calcium for an intracellular target. Angiotensin II‐stimulated migration was inhibited by pertussis toxin; from 71.6±2.0 μm in the absence, to 43.6±1.5 μm in the presence of pertussis toxin ( n =4, P <0.001). Migration of electroporated neutrophils stimulated by angiotensin II was synergistically enhanced by GTPγS. This suggests that one or more G‐proteins are involved in the activating effect of angiotensin II. Inhibitors of soluble guanylate cyclase and antagonists of cyclic GMP‐dependent kinase strongly inhibited the activating effect of angiotensin II. The results suggest that the activating effect of angiotensin II is mediated by cyclic GMP and by cyclic GMP‐dependent kinase.British Journal of Pharmacology (1997) 121 , 643–648; doi: 10.1038/sj.bjp.0701167