Evidence of an adriamycin binding site in the secretory granules of the mast cell

Decorti, Giuliana; Klugmann, Fiora Bartoli; Candussio, Luigi; Baldini, L

doi:10.1016/0009-2797(91)90106-h

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Adriamycin is another candidate for bind ing to mast cell granules: indeed, the antineoplastic drug Adriamycin is avidly taken up by mast cells only after these cells are induced to exocytose [17,18]. It is known that Adriamycin easily forms an ionic complex with hepa rin [19][20][21], with one molecule of heparin binding 16 molecules of Adriamycin [19], and hence it is conceivable that the drug binds to the heparin proteoglycan of mast cell gran ules.…”

Section: Discussionmentioning

confidence: 99%

Binding of Aminoglycoside Antibiotics by Degranulating Mast Cells

Decorti

Candussio²,

Klugmann³

et al. 1997

Chemotherapy

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The aminoglycoside antibiotics are polycationic at physiological pH and hence do not enter most cells. Indeed, when intact mast cells were incubated with gentamicin or tobramycin, extremely low concentrations of the two drugs could be measured. In contrast, when a controlled, specific degranulation of mast cells was induced by treating the cells with compound 48/80, Adriamycin or concanavalin A, a dose-dependent histamine release was observed and a significant increase of the intracellular concentrations of the aminoglycosides resulted. The uptake of gentamicin and tobramycin was not dependent on the type of stimulus, but was proportional to the quantity of histamine released. The aminoglycoside binding to granular material obtained from sonicated cells was similar to that of degranulating mast cells. These data suggest the occurrence of ionic interactions between the positively charged groups of the aminoglycosides and the negatively charged groups of granular matrix that are exposed as a consequence of exocytosis. The significance of this phenomenon is at present unclear but studies are in progress to clarify the fate of the aminoglycosides bound to mast cells.

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Section: Discussionmentioning

confidence: 99%

Binding of Aminoglycoside Antibiotics by Degranulating Mast Cells

Decorti

Candussio²,

Klugmann³

et al. 1997

Chemotherapy

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show abstract

“…Indeed, in mast cells adriamycin induces a significant, noncytotoxic histamine release that seems to play a role in adriamycin-induced cardiotoxicity (Klugmann et al 1986). The consequence of the exocytotic process is the externalization of a granular binding site for which adriamycin possesses an extraordinary affinity (Decorti et al 1991).…”

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confidence: 99%

“…lb) cells, without any inhibitory activity on adriamycin-induced histamine release (data not shown). Adriamycin exhibits an extraordinary affinity for mast cells; indeed, following exocytosis, a granular binding site is externalized, the nature of which is at present unclear (Decorti et al 1991). Specific binding of adriamycin to membrane lipids such as cardiolipin, phosphatidylserine and phosphatidic acid (Goormaghtigh et al 1987) has been demonstrated and it seems of interest that, following stimulation to secretion, in many secretory cells, including mast cell (Kennedy et al 1979) there is an extensive net conversion of phosphatidyl inositol to phosphatidic acid.…”

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confidence: 99%