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Polymorphonuclear leukocyte as a model of Ca++ and Mg++-dependent cellular activation. Effect of flunarizine
Abstract:
Flunarizine, a calcium entry blocker drug, concentration-dependently inhibited FMLP and A23187-induced aggregation, enzyme release and superoxide anion generation from human granulocytes. A23187-dependent granulocyte aggregation was also studied in media devoided of Ca++ or Mg++. Flunarizine (2.4 x 10(-5) M) significantly affected not only Ca++-supported but also Mg++-sustained granulocyte aggregation. The inhibiting effect of the drug was reversed by increasing extracellular level of Ca++ (1.2 mM) or Mg++ (2 mM). In this "in vitro" model, the role of flunarizine as a specific Mg++ entry blocker was suggested.
Insights
Flunarizine, a calcium entry blocker, inhibits human granulocyte aggregation and related functions. This study suggests flunarizine may also act as a magnesium (Mg++) entry blocker.
Area of Science:
- Pharmacology
- Immunology
- Cell Biology
Background:
- Flunarizine is a known calcium entry blocker.
- Granulocytes play a crucial role in inflammatory and immune responses.
- Cellular aggregation, enzyme release, and superoxide anion generation are key granulocyte functions.
Purpose of the Study:
- To investigate the effects of flunarizine on human granulocyte functions.
- To explore the potential role of flunarizine as a magnesium (Mg++) entry blocker.
Main Methods:
- Human granulocytes were treated with flunarizine.
- FMLP and A23187 were used to induce granulocyte aggregation, enzyme release, and superoxide anion generation.
- Experiments were conducted in media with varying concentrations of calcium (Ca++) and magnesium (Mg++).
Main Results:
- Flunarizine inhibited FMLP and A23187-induced granulocyte aggregation, enzyme release, and superoxide anion generation in a concentration-dependent manner.
- Flunarizine affected both calcium- and magnesium-supported granulocyte aggregation.
- The inhibitory effects of flunarizine were reversible by increasing extracellular Ca++ or Mg++ levels.
Conclusions:
- Flunarizine exhibits inhibitory effects on key human granulocyte functions.
- The findings suggest a potential role for flunarizine as a specific magnesium (Mg++) entry blocker in vitro.