Modulation of neutrophil migration by captopril.
Because neutrophils might be involved in some of the therapeutic effects of captopril we studied the effect of captopril on neutrophil migration. Captopril strongly enhances migration by rabbit peritoneal neutrophils. Stimulation by captopril was maximal at a concentration of about 400 microM; at higher concentrations stimulation decreased again. The stimulatory effect is partly chemokinetic, and partly chemotactic. Captopril disulfide also stimulates migration, though the stimulating effect is less than that of captopril. Captopril-induced stimulation of migration was strongly inhibited by pretreatment of neutrophils with pertussis toxin, indicating that the stimulation is mediated by a pertussis toxin-sensitive G protein. Intact sulfhydryl groups on the cell surface are required for stimulation because inactivation of these groups with the non-penetrating sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) completely abolishes the stimulating effect of captopril and of captopril disulfide. Both captopril and captopril disulfide cause an enhancement of cyclic GMP level in the neutrophil. The enhancement of both the cGMP level and that of migration is blocked by methylene blue and by LY-83583, suggesting that the stimulating effect of captopril is mediated by cGMP. Inhibitors of NO generation, such as NG-monomethyl-L-arginine, NG-nitro-L-arginine and canavanine have no effect on captopril-induced stimulation of migration, indicating that NO is not involved in the stimulating effect of captopril.
Department of Medical Biochemistry, University of Leiden, The Netherlands.
J G
JG
Elferink
B M
BM
de Koster
D000818:Animals; D002216:Captopril / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D037342:Pertussis Toxin; D011817:Rabbits; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D013439:Sulfhydryl Reagents; D010566:Virulence Factors, Bordetella; D002216:Captopril; D037342:Pertussis Toxin; D006152:Cyclic GMP