Studies on the anti-allergic mechanism of glucocorticoids in mice.
Glucocorticoids inhibit IgE antibody-mediated passive cutaneous anaphylaxis (PCA) and chemical mediator-induced cutaneous reactions elicited in the mouse ear. In the present study, we investigated the effect of actinomycin D, a protein synthesis inhibitor, on dexamethasone-caused inhibition of PCA and histamine-induced cutaneous reaction in the mouse ear. Tyrosine aminotransferase (TAT) activity in the liver, which was estimated as an index for protein synthesis, significantly increased by the administration of hydrocortisone, prednisolone and dexamethasone. Significant increase in TAT activity was observed from 2 h after glucocorticoid administration and peaked at 4 h, and declined gradually thereafter. Cycloheximide even at high doses of 100 and 300 mg/kg failed to affect the increase in TAT activity by dexamethasone. On the contrary, actinomycin D at doses of 1 and 10 mg/kg abrogated the TAT activity increase by dexamethasone almost completely. Treatment with 1 mg/kg of actinomycin D, however, failed to affect the inhibition of PCA and histamine-induced cutaneous reaction by dexamethasone. These results suggest that glucocorticoids exhibit their inhibitory action of PCA and chemical mediator-induced cutaneous reactions in mice through a mechanism resistant to actinomycin D treatment.
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
N
N
Inagaki
T
T
Miura
T
T
Nakajima
K
K
Yoshida
H
H
Nagai
A
A
Koda
D000818:Animals; D001200:Ascaris / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000517:prevention & control*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D014444:Tyrosine Transaminase / Q000378:metabolism
D005938:Glucocorticoids; D003609:Dactinomycin; D003907:Dexamethasone; D006632:Histamine; D003513:Cycloheximide; D014444:Tyrosine Transaminase