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Inflammation Research

, Volume 46, Issue 4, pp 119–124 | Cite as

The antineoplastic drug vinorelbine activates non-immunological histamine release from rat mast cells

  • M. D. Estévez
  • M. R. Vieytes
  • M. C. Louzao
  • A. Alfonso
  • N. Vilariño
  • L. M. Botana

Abstract.

Objective and Design: We explore the mechanism of the antineoplastic drug vinorelbine activation in its rat mast cell exocytosis.¶Materials: The study was carried out on mast cells obtained from Sprague-Dawley rats.¶Treatment: Vinorelbine (5–100<mu>g/mL), cholera toxin (200 ng/mL), pertussis toxin (100 ng/mL), benzalkonium chloride (10 <mu>g/mL), compound 48/80 (1 <mu>g/mL), okadaic acid (1 <mu>M), 12-tetradecanoate-acetate (50 ng/ml), perphenazine (1 <mu>g/ml), theophylline (10 mM), IBMX (1 mM), rolipram (15 <mu>M).¶Methods: Histamine release was measured fluorimetrically.¶Results: The drugs that modify G-protein activity, cholera toxin, pertussis toxin or benzalkonium chloride, do not modify the response profile. The exocytosis elicited by compound 48/80 is decreased by Gs or Gi modulation, which suggests that G proteins are not involved in vinorelbine stimulated secretion. The phosphatase inhibitor okadaic acid shows no effect on vinorelbine-stimulated release, nor on the activation or inhibition of protein kinase C with phorbol 12-tetradecanoate-acetate or perphenazine. The unspecific phosphodiesterase inhibitors theophylline and IBMX inhibited histamine release, but not the phosphodiesterase IV inhibitor rolipram.¶Conclusions: The overall results show that vinorelbine activates histamine release through a rather selective mechanism that may be mediated by certain phosphodiesterase-dependent transduction pathways.

Key words: Mast cells — Histamine release — Vinorelbine — Signal transduction 

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Copyright information

© Birkhäuser Verlag, Basel, 1997

Authors and Affiliations

  • M. D. Estévez
    • 1
  • M. R. Vieytes
    • 2
  • M. C. Louzao
    • 1
  • A. Alfonso
    • 1
  • N. Vilariño
    • 1
  • L. M. Botana
    • 1
  1. 1.Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago, E-27002 Lugo, SpainES
  2. 2.Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago, E-27002 Lugo, SpainES

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