Inhibition of immunoglobulin, but not polypeptide base-stimulated release of histamine and arachidonic acid by anti-inflammatory steroids.
Incubation overnight of purified rat mast cells with glucocorticoids inhibited the release of histamine and [1-14C]arachidonic acid (and its metabolites) stimulated by three immunoglobulin (Ig) E-like secretagogues, anti-IgE, the antigen-ovalbumin and concanavalin A. In contrast, pretreatment with glucocorticoids did not affect either histamine or [1-14C]arachidonic acid release stimulated by somatostatin, compound 48/80 or the calcium ionophore A23187. Glucocorticoids inhibited IgE-like arachidonic acid and histamine release with an order of potency similar to their in vivo anti-inflammatory potencies (i.e., fluocinolone greater than dexamethasone greater than hydrocortisone greater than cortisone). This inhibition required several hours and was temperature-dependent, suggesting a specific glucocorticoid receptor mechanism. IgE-stimulated Ca++ influx was decreased by hydrocortisone pretreatment. These results suggest that glucocorticoids specifically uncouple IgE-mediated calcium flux with subsequent inhibition of histamine and arachidonic acid release.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology; D007073:Immunoglobulin E / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005938:Glucocorticoids; D010455:Peptides; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D013004:Somatostatin; D006854:Hydrocortisone