Delayed anti-inflammatory action of nedocromil sodium in the rat paw is dependent on de novo protein synthesis.
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.
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
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012702:Serotonin Antagonists; D017835:Nedocromil; D003907:Dexamethasone