Mitoxantrone induces nonimmunological histamine release from rat mast cells.
The antineoplastic drug mitoxantrone (MTX) elicits a fast noncytotoxic and nonimmunological histamine release from peritoneal and pleural rat mast cells. The non specific phosphodiesterase inhibitor isobuthyl-methylxantine (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 microM) 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 micrograms/ mL). The inhibition of protein phosphatases 1 and 2A by okadaic acid (1 microM) 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.
Estévez
M D
MD
Departamento de Farmacología, Facultad de Veterinaria, Lugo, Spain.
Vieytes
M R
MR
Botana
L M
LM
D015056:1-Methyl-3-isobutylxanthine / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity; D004988:Ethers, Cyclic / Q000633:toxicity; D005089:Exocytosis / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D019319:Okadaic Acid; D010529:Peritoneal Cavity / Q000166:cytology; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity; D010994:Pleura / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D013806:Theophylline / Q000633:toxicity; D014268:Trifluoperazine / Q000633:toxicity; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000970:Antineoplastic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D010726:Phosphodiesterase Inhibitors; D019319:Okadaic Acid; D014268:Trifluoperazine; D003189:p-Methoxy-N-methylphenethylamine; D008942:Mitoxantrone; D013806:Theophylline; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine