STUDY OF THE ACTIVATION MECHANISM OF ADRIAMYCIN ON RAT MAST-CELLS

Adriamycin (ADR) induces nonimmunological and noncytotoxic histamine r elease from peritoneal and pleural rat mast cells. This secretion is u naffected by the pretreatment with pertussis toxin, cholera toxin and benzalkonium chloride. Histamine release induced by compound 48/80, wa s markedly inhibited by pertussis toxin, cholera toxin, benzalkonium c hloride and neuraminidase. The ADR dose-response curve is significantl y shifted to the right when cells were preincubated with the unspecifi c phosphodiesterase inhibitor IBMX. The activation of protein kinase C (PKC) with the phorbol esther TPA increases the response to ADR, whil e PKC inhibition with trifluoperazine decreases histamine release. The pretreatment of mast cells with okadaic acid did not modify the respo nse to ADR. These results suggests that ADR elicits histamine release with a mechanism notably different from compound 48/80.