title: Delayed anti-inflammatory action of nedocromil sodium in the rat paw is dependent on de novo protein synthesis.
abstract: Nedocromil sodium is commonly suggested to reduce allergic inflammation by inhibiting mediator release from mast cells. However, nedocromil also exhibits a wide range of additional anti-inflammatory activities, including inhibition of increased vascular permeability induced by individual mediators such as histamine. In the present study, we have further characterized the mode of action of nedocromil in a rat model for hind paw edema. Mast cell-dependent edema was induced with compound 48/80 (edema response mainly due to 5-hydroxytryptamine release), and direct mediator-induced plasma extravasation was evoked by exogenous 5-hydroxytryptamine (both agents injected locally). Local pretreatment with nedocromil for 20 min dose-dependently inhibited the edema evoked by compound 48/80 more effectively than that induced by 5-hydroxytryptamine. However, after 2 h pretreatment, both the 5-hydroxytryptamine-and compound 48/80-induced edema responses were inhibited to approximately the same extent by a range of concentrations of nedocromil, as well as by dexamethasone. Local inhibition of RNA/protein synthesis with actinomycin-D abolished the effects of both dexamethasone and nedocromil (2 h local pretreatment). We thus conclude that nedocromil can produce an 'anti-exudative' effect that is independent of inhibition of mast cell mediator release, is slow in onset, and requires de novo protein synthesis.
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D017835:Nedocromil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012702:Serotonin Antagonists; D017835:Nedocromil; D003907:Dexamethasone