Drug Disodium Cromoglycate Research Articles

Mucosal mast cells: III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells

Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin, apigenin, chrysin, and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Effect of cyclic AMP, disodium cromoglycate and other anti-allergic drugs on histamine secretion from rat mast cells stimulated with the calcium ionophore ionomycin.

Cyclic AMP analogues and the anti-allergic drugs disodium cromoglycate, quercetin, doxantrazole and theophylline inhibited histamine secretion from rat peritoneal mast cells stimulated with the calcium ionophore ionomycin. The potency of the compounds varied inversely with the concentration of ionophore and with the period of incubation. The drugs were active in both the presence and absence of extracellular calcium. These results cannot be explained in terms of the postulated effect of the compounds on the receptor-mediated activation of calcium-channels. Alternative mechanisms for their action are thus considered.

Effect of anti-allergic and cyclic AMP-active drugs on histamine secretion from rat mast cells treated with the novel calcium ionophore chlortetracycline.

The anti-allergic drugs disodium cromoglycate, doxantrazole and quercetin, and a number of compounds known to elevate intracellular levels of cyclic AMP, inhibited histamine secretion from rat peritoneal mast cells stimulated with the novel calcium ionophore, chlortetracycline. The potency of the compounds varied inversely with the concentration of ionophore. The activity of the drugs cannot be explained in terms of their postulated effect on the receptor-mediated activation of calcium channels in the mast cell membrane. Alternative mechanisms for their action are thus considered.

Inhibition of allogeneic reactions with the anti-allergic drug disodium cromoglycate: [formula omitted], Blond McIndoe Centre for Transplantation Biology, Queen Victoria Hospital, East Grinstead, Sussex, U.K.

Inhibition of allogeneic reactions with the anti-allergic drug disodium cromoglycate: [formula omitted], Blond McIndoe Centre for Transplantation Biology, Queen Victoria Hospital, East Grinstead, Sussex, U.K.

Inhibition of histamine release from rat peritoneal mast cells treated with the ionophore A23187. Implications for the mode of action of anti-allergic compounds.

Cyclic AMP and the anti-allergic drugs disodium cromoglycate (DSCG), quercetin, doxantrazole, and theophylline, inhibit histamine release induced by the ionophore A23187 in both the presence and the absence of extracellular calcium. These results cannot be explained in terms of the postulated effect of the drugs on the calcium-gating mechanism activated by the anaphylactic reaction. Alternative mechanisms of action of the compounds are thus considered.

Inhibition of in vitro allogeneic reactions with disodium cromoglycate.

The antiallergic drug disodium cromoglycate (DSCG) selectively inhibits allogeneic responses in mixed lymphocyte culture (MLC) reactions, but does not affect cell viability or suppress lymphocyte responses to mitogens. Preincubation experiments with DSCG were without effect, indicating that the drug does not bind to unstimulated lymphocytes. Timed studies demonstrated maximal MLC inhibition when DSCG was added during the first 12 h or culture and no effect if added later than 72 h. Both natural killing and cell-mediated lympholysis (CML) assays proceeded normally in the presence of optimal MLC-inhibitory concentrations of DSCG. CML reactions were eliminated, however, by the presence of drug during generation of cytotoxic T cells. The proposed mode of action for DSCG is blocking of calcium influx across cell membranes, thereby inhibiting the release of mast cell and basophil granules in hypersensitivity reactions. Such a mechanism would seem unlikely for DSCG-mediated lymphocyte effects as several calcium-dependent lymphocyte functions are not obstructed.

Role of contractile microfilaments in the release of histamine from mast cells.

THE release of histamine and other mediators of immediate type anaphylactic reactions from mast cells is triggered by the interaction of antigen with cell-bound antibody. Antigen-induced histamine release and that induced by Compound 48/80 are energy-dependent processes which are depressed by metabolic inhibitors and follow a similar time course1–3. This type of selective release of histamine is inhibited by the potent anti-asthmatic drug disodium cromoglycate (DSCG)4, whereas the non-selective release induced by agents such as the detergent ‘Triton X-100’, which follows a different time course and is not energy dependent, is not blocked by DSCG. It has therefore been postulated4,5 that histamine is released from mast cells by two distinct mechanisms: a selective release of amine-containing granules through a process of exocytosis, and a non-selective release of amines and other cellular constituents as a result of lysis of cell membranes.