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The inhibitory effect of phenothiazine stains on rat and guinea-pig mast cell damage induced by antihistamines and compound 48/80

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Summary

  1. 1.

    Toluidine blue inhibits rat mesentery mast cell disruption induced by compound 48/80 and by the antihistamine drugs chlorcyclizine and diphenhydramine.

  2. 2.

    Glucose reverses the blocking action of toluidine blue. Calcium does not.

  3. 3.

    In the guinea-pig mesentery, mast cell damage induced by promethazine is inhibited by toluidine blue. Glucose does not reverse this blocking action. Damage by compound 48/80 is not inhibited.

  4. 4.

    Two other phenothiazine stains—methylene blue and thionin—also inhibit rat mesentery mast cell damage by compound 48/80. For its inhibiting action thionin requires a much lower concentration than the other two dyes.

  5. 5.

    The action of methylene blue and thionin on rat mast cells is influenced by the pH of the incubation medium. Much higher concentrations of these stains are needed to protect mast cells from the action of compound 48/80 when the pH is lowered from 8.4 to 7.0. Toluidine blue, however, is not influenced by pH changes.

  6. 6.

    “In vitro” staining of mast cells with methylene blue and thionin is also influenced by pH. At 8.4 the cells are well stained, while at 7.0 they are barely stained at all.

  7. 7.

    It is concluded that phenothiazine stains block mast cell damage by inhibiting cell metabolism. Therefore, besides its lytic action, antihistamines must also act through an energy-requiring process similar to that of compound 48/80. In the guinea-pig, promethazine damages mast cells through a mechanism different from that of compound 48/80, although both are non energy-requiring. Either in the rat or in the guinea-pig the phenothiazine stains do not seem to inhibit the action of mast cell damaging agents by blocking their access to the active cell sites.

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Vugman, I., do Prado, M.L.M. The inhibitory effect of phenothiazine stains on rat and guinea-pig mast cell damage induced by antihistamines and compound 48/80. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 173–184 (1973). https://doi.org/10.1007/BF00503981

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