Evidence of an adriamycin binding site in the secretory granules of the mast cell.
Adriamycin induced significant non-cytotoxic histamine release from rat peritoneal mast cells to which the drug showed a very high affinity. The relationship between adriamycin-induced exocytosis and its uptake by purified rat peritoneal mast cells was studied. Adriamycin induced histamine release and was highly concentrated in mast cells at 37 degrees C but not at 0 degrees C. However, if exocytosis was provoked by other secretagogues like compound 48/80, protamine, concanavalin A, and ionophore A23187, and cells were then treated with adriamycin at 0 degrees C, the concentrations of the antineoplastic drug significantly increased. Adriamycin binding to purified granular material was similar to that of intact cells treated at 37 degrees C, but was not modified by metabolic inhibitors, extremes of temperature (0 or 45 degrees C) or by the carboxylic ionophore monensin. On the contrary, sodium cromoglycate limited adriamycin binding to granular materials as well. In addition, sodium cromoglycate, but not monensin, displaced the antineoplastic drug from mast cells, even when added after adriamycin. We conclude that the high affinity of adriamycin for mast cells is ascribable to the externalization of a granular binding site, as a consequence of the exocytotic process. The experiments with sodium cromoglycate suggest that this binding site could be in common with the antiallergic drug.
Decorti
G
G
Institute of Pharmacology, Faculty of Medicine, University of Trieste, Italy.
Klugmann
F B
FB
Candussio
L
L
Baldini
L
L
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001665:Binding Sites; D004317:Doxorubicin / Q000378:metabolism* / Q000493:pharmacokinetics; D005089:Exocytosis / Q000502:physiology; D005976:Glutaral / Q000494:pharmacology; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013010:Sonication; D013696:Temperature; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003189:p-Methoxy-N-methylphenethylamine; D000968:Antimycin A; D004317:Doxorubicin; D008985:Monensin; D005976:Glutaral