Effects of non-steroidal anti-inflammatory drugs and cyclooxygenase-2 specific inhibitors on mediator release from rat peritoneal mast cells

Comparison of the influence of NSAIDs with different COX-selectivity on histamine release from mast cells isolated from naïve and sensitized rats

“…at concentrations more than 100 times less than found here. The inhibition of PG-synthesis [11,13,14] took place over hours and it is thus possible that short term preincubation does not allow the drug to access relevant intracellular domains, as also indicated by earlier data of no effect on the PGD 2 synthesis in relation to histamine release [8]. Our preliminary observations with NS-398 of inhibition even without preincubation support this possibility.…”

“…These apparently conflicting results may be a reflection of the inconsistencies in previous reports of the influence of NSAID on histamine release from rat mast cells [5][6][7][8]. Mast cells do produce PGD 2 in connection with histamine release [8,9] but there does not seem to be a firm correlation between the release of these two mediators in terms of neither time course or magnitude of response relative to intensity and nature of stimulus [9,10,25,26] nor susceptibility to COX- inhibitors [8,[27][28][29].…”

“…Mast cells do produce PGD 2 in connection with histamine release [8,9] but there does not seem to be a firm correlation between the release of these two mediators in terms of neither time course or magnitude of response relative to intensity and nature of stimulus [9,10,25,26] nor susceptibility to COX- inhibitors [8,[27][28][29]. In the latter context it is relevant to consider various aspects of the pharmacology of NSAID.…”

“…In addition, functional links between the different mediators as well as individual pathways for their production have been investigated with a variety of approaches, sometimes with contradictory results, e.g. of the influence of non-steroidal anti-inflammatory drugs (NSAID) on histamine release from rat peritoneal mast cells with findings of a pronounced inhibition [5], a variable inhibition [6,7], and of no inhibition despite a substantial inhibition of prostaglandin D 2 (PGD 2 ) synthesis [8].…”

Dual effects of acetylsalicylic acid on mast cell degranulation, expression of cyclooxygenase-2 and release of pro-inflammatory cytokines

“…It is at these concentrations that NSAIDs have been reported to inhibit COX enzyme activity [37] but not gene expression [38].…”