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Mitoxantrone induces nonimmunological histamine release from rat mast cells

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Abstract

The antineoplastic drug mitoxantrone (MTX) elicits a fast nocytotoxic and nonimmunological histamine release from peritoneal and pleural rat mast cells. The non specific phosphodiesterase inhibitor isobuthylmethylxantine (1 mM) decreases the potency of MTX. Theophylline (10 mM) decreases both the potency and the efficacy of MTX-induced histamine secretion. The protein kinase C (PKC) activator, tetradecanoyl-phorbol-13-acetate (50 ng/mL), enhances the effect of MTX, whereas the non specific PKC inhibitor trifluoperazine (10 μM) exerts no effect.

Histamine release was also unaffected by substances acting on G-proteins, namely pertussis toxin (200 ng/mL), cholera toxin (300 mg/mL) and benzalkonium chloride (10 μg/mL). The inhibition of protein phosphatases 1 and 2A by okadaic acid (1 μM) does not modify the response. The results indicate that mitoxantrone elicits the exocytosis in mast cells by a mechanism similar to the parent compound adriamycine, but different to the polyamine compound 48/80.

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Authors and Affiliations

  1. Departmento de Farmacología, Facultad de Veterinaria, E-27002, Lugo, Spain

    M. D. Estévez & L. M. Botana

  2. Departmento de Fisiologá, Facultad de Veterinaria, E-27002, Lugo, Spain

    M. R. Vieytes

Authors
  1. M. D. Estévez
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  2. M. R. Vieytes
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  3. L. M. Botana
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accepted by W. Lorenz

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Estévez, M.D., Vieytes, M.R. & Botana, L.M. Mitoxantrone induces nonimmunological histamine release from rat mast cells. Inflamm Res 45, 113–117 (1996). https://doi.org/10.1007/BF02265162

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  • DOI: https://doi.org/10.1007/BF02265162

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