Comparative studies on the effect of non-steroidal antiinflammatory drugs (NSAID) on histamine release from mast cells of the rat and guinea pig

Abstract

The effects of a number of non-steroidal anti-inflammatory drugs (NSAID) on histamine secretion from tissue mast cells of the rat and the guinea pig have been examined. According to the experimental conditions and cell type, the drugs potentiated, inhibited or had no effect on histamine release. The possible mechanisms of these effects are discussed.

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

“…This contradicts previous reports which observed significant inhibition [3][4][5]. The discrepancy maybe due to the high concentrations (>0.5 mM) of NSAIDs or the effects of contaminating cells in the mixed peritoneal cells used in these studies.…”

“…Hence agents which selectively inhibit COX-2 have been synthesized in order to produce anti-inflammatory drugs devoid of the side effects of NSAIDs [1,2]. Although reports on the effects of NSAIDs on mast cell mediator release have previously been published, results are contradicting [3][4][5]. With the introduction of selective COX-2 inhibitors, it is the aim of the present study to compare the effects of NSAIDs and COX-2 inhibitors on histamine and prostaglandin 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

“…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].…”

“…In the latter context it is relevant to consider various aspects of the pharmacology of NSAID. Both selectivity and specificity are of particular concern when the activity of NSAIDs takes place at concentrations as high as observed in the present as well as in other mast cell studies [5][6][7]30].…”

“…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].…”