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Inhibition by actinomycin D of neurogenic mouse ear oedema

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Abstract

We have investigated the effects of actinomycin D on mouse ear oedema induced by capsaicin, neuropeptides, and established inflammatory mediators. Actinomycin D (0.5 mg/kg, i.v.) significantly (P < 0.01) inhibited ear oedema induced by topical application of capsaicin, while adriamycin (6.0 mg/kg, i.v.) and cycloheximide (6.0 mg/kg, i.v.) had no effect on oedema. The ear oedema induced by intradermal injection of neuropeptides such as mammalian tachykinins, calcitonin generelated peptide (CGRP), and vasoactive intestinal peptide (VIP), was markedly (P < 0.05, P < 0.01 or P < 0.001) suppressed by actinomycin D. The drug was also effective (P < 0.01 or P < 0.001) in inhibiting bradykinin (BK)-and compound 48/80-induced ear oedema, but did not inhibit oedema induced by histamine, 5-HT, leukotriene C4 (LTC4), and platelet activating factor (PAF) at a dose of 1 mg/kg. In mast cell-deficient W/Wv mice, actinomycin D (1.0 mg/kg, i.v.) failed to inhibit substance P (SP)-induced ear oedema whereas spantide (0.5 mg/kg, i.v.) was an effective (P < 0.01) inhibitor of oedema formation. Furthermore, actinomycin D (10–100 µM) dosedependently prevented histamine release from rat peritoneal mast cells evoked by SP, compound 48/80, and the ionophore A23182, respectively. These results strongly suggest that an inhibitory effect of actinomycin D on neurogenic inflammation is due primarily to the prevention of mast cell activation mediated by neuropeptides, rather than an interaction with DNA or receptors of neuropeptides.

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Authors and Affiliations

  1. Research Laboratory, Minophagen Pharmaceutical Co., 2-5233, Komatsubara, Zama, 228, Kanagawa, Japan

    Hideo Inoue & Nobuyuki Nagata

  2. Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Sakaecho, Itabasi-ku, 173, Tokyo, Japan

    Yasuko Koshihara

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  1. Hideo Inoue
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  2. Nobuyuki Nagata
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  3. Yasuko Koshihara
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Inoue, H., Nagata, N. & Koshihara, Y. Inhibition by actinomycin D of neurogenic mouse ear oedema. Inflamm Res 44, 125–130 (1995). https://doi.org/10.1007/BF01782023

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  • DOI: https://doi.org/10.1007/BF01782023

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