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.
Inoue
H
H
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Nagata
N
N
Koshihara
Y
Y
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000633:toxicity; D000001:Calcimycin / Q000008:administration & dosage / Q000633:toxicity; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000633:toxicity; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity; D003513:Cycloheximide / Q000008:administration & dosage / Q000633:toxicity; D003609:Dactinomycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004427:Ear Diseases / Q000188:drug therapy; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006632:Histamine / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D007275:Injections, Intravenous; D017997:Leukotriene C4 / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage / Q000633:toxicity; D013373:Substance P / Q000008:administration & dosage / Q000633:toxicity; D015320:Tachykinins / Q000008:administration & dosage / Q000633:toxicity; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000633:toxicity; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000633:toxicity
D010972:Platelet Activating Factor; D015320:Tachykinins; D003609:Dactinomycin; D017997:Leukotriene C4; D012701:Serotonin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D004317:Doxorubicin; D006632:Histamine; D003513:Cycloheximide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin