Study of the activation mechanism of adriamycin on rat mast cells.
Adriamycin (ADR) induces nonimmunological and noncytotoxic histamine release from peritoneal and pleural rat mast cells. This secretion is unaffected by the pretreatment with pertussis toxin, cholera toxin and benzalkonium chloride. Histamine release induced by compound 48/80, was markedly inhibited by pertussis toxin, cholera toxin, benzalkonium chloride and neuraminidase. The ADR dose-response curve is significantly shifted to the right when cells were preincubated with the unspecific phosphodiesterase inhibitor IBMX. The activation of protein kinase C (PKC) with the phorbol esther TPA increases the response to ADR, while PKC inhibition with trifluoperazine decreases histamine release. The pretreatment of mast cells with okadaic acid did not modify the response to ADR. These results suggest that ADR elicits histamine release with a mechanism notably different from 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 / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001548:Benzalkonium Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects*; D019319:Okadaic Acid; D010529:Peritoneal Cavity / Q000166:cytology; D037342:Pertussis Toxin; D010994:Pleura / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001548:Benzalkonium Compounds; D004988:Ethers, Cyclic; D010566:Virulence Factors, Bordetella; D019319:Okadaic Acid; D014268:Trifluoperazine; D000968:Antimycin A; D004317:Doxorubicin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine