Inhibition by actinomycin D of neurogenic mouse ear oedema.

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 gene-related 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 microM) dose-dependently 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.