The Inhibition of Histamine Release From Rat Peritoneal Mast Cells by Non‐steroid Anti‐inflammatory Drugs and Its Reversal by Calcium

Abstract

1The non-steroid anti-inflammatory drugs, indomethacin, flufenamate and meclofenamate, inhibited the release of histamine from rat peritoneal mast cells induced by pharmacological or immunological challenge in vitro. 2 Anti-inflammatory steroids had little effect on histamine release from the mast cells. 3 Th inhibition of histamine release by the aspirin-like drugs was not prevented by incubation with glucose, unlike the inhibition of 2,4,dinitrophenol or antimycin-A. This suggests that the non-steroid anti-inflammatory compounds do not act by preventing the energy production from oxidative metabolism, required for histamine release. 4 The inhibition of the calcium ionophore A23187-induced histamine release by the aspirin-like drugs was reversed by an increase in the calcium concentration of the incubation medium. 5 The results suggest that the non-steroid anti-inflammatory compounds inhibit histamine release by actions on calcium influx into the mast cell, or on calcium mobilization or utilization within the mast cell.

Influence of glucocorticoids on histamine release and45Calcium uptake by isolated rat mast cells

“…The present observations are in accordance with earlier findings under similar conditions (i.e. pharmacological concentrations of the glucocorticoids and brief preincubation) with mast cells [16,17], antigen-induced histamine release from human skin slices [13], and human lung in lo. ~ 8. vitro [14], function of human polymorphonuclear leukocytes [20][21][22][23], and platelet aggregation in vitro and in vivo [24][25][26].…”

“…from basophils [12], skin slices [131, and lung in vitro {141 and in vivo [15[. The ability of the glucocorticoids to inhibit histamine release from mast cells has been demonstrated with rat peritoneal cells [16,17[, but the information available is scarce. The aim of the present investigation is to provide a more complete picture of the inhibitory effects of the glucocorticoids in order to gain insight into their mode of action.…”

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.…”

Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

“…These earlier findings explain why in the present study actinomycin D prevented the inhibition of the aldosterone-mediated effect on recovery. Likewise, prostaglandin E 2 potentiates histamine release (40) and indomethacin inhibits degranulation of isolated rat peritoneal mast cells (11,18). The inhibition by indomethacin on the effect of aldosterone on recovery may be due to a similar effect on the mast cells localized in the vascular wall.…”