Polymorphonuclear leucocytes as a model of Ca++ and Mg++-dependent cellular activation. Effect of calcium entry blockers.
Flunarizine inhibited FMLP- and A23187-induced aggregation, enzyme release and O2- generation from human PMN as a function of its concentration. A23187-dependent PMN aggregation was also studied in media devoid of Ca++ or Mg++. Flunarizine (2.4 X 10(-5)M) significantly affected not only Ca++-supported but also Mg++-sustained PMN aggregation. The inhibiting effect of the drug was reversed by increasing the level of Ca++ (1.2 mM) or Mg++ (2 mM). Nifedipine, another Ca++-entry blocker, was shown to inhibit enzyme release and O2- generation induced by FMLP and A23187 as a function of its concentration, but only slightly affected PMN aggregation at very high concentration (10(-4)M). A role for flunarizine as a specific Mg++-entry blocker is suggested.
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects; D002936:Cinnarizine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005444:Flunarizine; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D000001:Calcimycin; D002936:Cinnarizine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase; D005966:Glucuronidase; D008274:Magnesium; D009543:Nifedipine; D005444:Flunarizine; D002118:Calcium