Article date: June 1997
By: Jan G. R. Elferink, Ben M. Koster, in Volume 121, Issue 4, pages 643-648
Angiotensin II had a bimodal effect on human neutrophil migration. Low concentrations of angiotensin II stimulated random migration. At a concentration of 10−10M 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 10−10M 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 10−8M and higher inhibited chemotactic peptide‐stimulated chemotaxis.
The stimulant effect of angiotensin II on migration was completely dependent on extracellular Ca2+. In the presence of 1 mM Ca2+, angiotensin II stimulated migration to 76.1±1.7 μm, while migration in the absence of Ca2+ 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 Ca2+ than in electroporated cells. This supports the view that there is an influx of Ca2+ 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.
Angiotensin II had a bimodal effect on human neutrophil migration. Low concentrations of angiotensin II stimulated random migration. At a concentration of 10−10M 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 10−10M 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 10−8M and higher inhibited chemotactic peptide‐stimulated chemotaxis.
The stimulant effect of angiotensin II on migration was completely dependent on extracellular Ca2+. In the presence of 1 mM Ca2+, angiotensin II stimulated migration to 76.1±1.7 μm, while migration in the absence of Ca2+ 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 Ca2+ than in electroporated cells. This supports the view that there is an influx of Ca2+ 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
DOI: 10.1038/sj.bjp.0701167
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