Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: Implications for its mode of action

Chand, N.; Pillar, J.; Diamantis, W.; Perhach, James L.; Sofia, R. D.

doi:10.1016/0014-2999(83)90311-4

Cited by 123 publications

(36 citation statements)

References 8 publications

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“…When calcium ionophore A23187 was used as a secretagogue, Trisgel C buffer was used, and peritoneal mast cells were obtained from nonsensitized rats. (Chand et al, 1983a).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of allergic and non‐allergic histamine secretion from rat peritoneal mast cells by calcium antagonists

Chand

Diamantis

Pillar

et al. 1984

British J Pharmacology

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Bepridil, TMB‐8 (8‐(diethylamino)octyl 3,4,5‐trimethoxybenzoate hydrochloride),diltiazem, verapamil and nifedipine exerted concentration‐dependent inhibition of antigen and calcium ionophore A23187‐induced histamine release from rat peritoneal mast cells. The inhibitory effects of verapamil and bepridil against calcium ionophore A23187‐induced histamine secretion were antagonized by increased Ca2+ concentrations in the extracellular medium. These observations suggest that both agents act by interfering with the influx of Ca2+ into the mast cells. The inhibitory activities of five different Ca2+ channel blockers on allergic and non‐allergic histamine secretion from rat peritoneal mast cells varied considerably depending upon the nature of the secretagogue as well as concentration and type of Ca2+‐antagonist examined.

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“…When calcium ionophore A23187 was used as a secretagogue, Trisgel C buffer was used, and peritoneal mast cells were obtained from nonsensitized rats. (Chand et al, 1983a).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of allergic and non‐allergic histamine secretion from rat peritoneal mast cells by calcium antagonists

Chand

Diamantis

Pillar

et al. 1984

British J Pharmacology

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“…Aerosolized azelastine administered immediately or 15 min before antigen challenge effectively inhibits lung anaphylactic responses, i.e., decline in dynamic lung compliance and increase in airway resistance (Chand et al, 1985a). These observations suggest that azelastine exerts rapid and selective inhibitory effects on the synthesis/release of chemical mediators from mast cells (basophils, leukocytes), perhaps by interfering with a Ca2+-dependent step in target cells of allergic inflammation (Chand et al, 1983b).…”

Section: Pharmacological Modulation Ofschultz-dale Responses In Guinementioning

confidence: 93%

“…On the contrary, azelastine inhibits antigen-, A23187-and concanavalin A-stimulated histamine secretion from mast cells even when added simultaneously or immediately prior to the addition of the secretagogues to the cell suspensions with an IC50 of 7 to 8.8 pM (Chand et al, 1983b;1985b,c;Fields et al, 1984). Aerosolized azelastine administered immediately or 15 min before antigen challenge effectively inhibits lung anaphylactic responses, i.e., decline in dynamic lung compliance and increase in airway resistance (Chand et al, 1985a).…”

Section: Pharmacological Modulation Ofschultz-dale Responses In Guinementioning

confidence: 96%

“…Azelastine inhibits passive cutaneous anaphylaxis and allergic bronchoconstriction (Zechel et al, 1981;Katayama et al, 1981;Mandi et al, 1981;Diamantis et al, 1984a,b;Perhach et al, 1984;Chand et al, 1984Chand et al, , 1985aAtkins et al, 1985;Storms et al, 1985). It inhibits allergic and nonallergic release of histamine (Chand et al, 1983b;1985b,c;Fields et al, 1984). Azelastine has also been shown to inhibit the allergic release of slow reacting substance of anaphylaxis (SRS-A, leukotrienes) during passive peritoneal anaphylaxis in rats as wejl as calcium 'Author for correspondence: Wallace Laboratories, Box 1, Cranbury, New Jersey 08512, U.S.A. ionophore A23187-stimulated release of SRS (leukotrienes) from rat isolated mixed peritoneal cells (Diamantis et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of in vitro anaphylaxis of guinea‐pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs

Chand

Diamantis

Sofia

1986

British J Pharmacology

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1 The ability of azelastine to influence antigen-induced contractile responses (Schultz-Dale phenomenon) in isolated tracheal segments of the guinea-pig was investigated and compared with selected antiallergic drugs and inhibitors of arachidonic acid metabolism. 2 Indomethacin produced a significant leftward shift of the antigen concentration-effect curve. 3 The inhibitory activity ofazelastine on anaphylactic responses in guinea-pig trachea was dependent on the duration of exposure (preincubation period). 4 The relative order ofpotency (antianaphylactic activity) at calculated IC50 level was as follows: FPL 55712 (a leukotriene receptor antagonist) > nordihydroguaiaretic acid (a lipoxygenase inhibitor) > pbromophenacyl bromide (a phospholipase A2 inhibitor) > BW 755c (a dual inhibitor of lipoxygenase and cyclo-oxygenase) > theophylline (a phosphodiesterase inhibitor) > azelastine > diphenhydramine (HI histamine-receptor antagonist) > ketotifen > disodium cromoglycate. FPL 55712 (added 5 min before antigen challenge) was about 12 times as potent as azelastine (added 2 h before antigen challenge). 5 The incubation of tracheal segments with azelastine and BW 755c for a period of 30 min was found to inhibit indomethacin-augmented anaphylactic responses. These observations seem to suggest that azelastine and BW 755c interfere with the synthesis/release ofthe products oflipoxygenase/leukotriene synthetase pathway (e.g., leukotrienes) in the mediation of allergic responses in airway smooth muscles.

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“…It was reported that this agent inhibits the release of chemical mediators from rat peritoneal mast cells [ 1 ] and stabilizes cell membranes [2] . We recently found that azelastine partially circumvents the resistance to adriamycin (ADM) of ADM-resistant sublines (P388/ADM; K562/ADM) of the P388 murine leukemia cell line (P388) and the K562 human leukemia cell line (K562) [3] .…”

mentioning

confidence: 99%

Circumvention of Multidrug Resistance of Leukemia Cells by the Anti-Allergic Agent Azelastine.

Fukuda¹,

Hui²,

Yamamoto³

et al. 1993

J. Clin. Biochem. Nutr.

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SummaryAzelastine, an anti-allergic agent, completely overcame the resistance to vincristine (VCR) of a VCR-resistant subline (P388/VCR) of P388 murine leukemia cells (P388). Considering our previous result [ Yamamoto et al. (1989) J. Glin. Biochem. Nutr., 6, 205] that the drug overcame the resistance to adriamycin (ADM) of an ADM-resistant subline (P388/ADM) of P388, we concluded that the drug circumvents multidrug resistance of leukemia cells. This circumvention by azelastine is ascribable to the accumulation of anticancer agent in drug-resistant leukemia cells. As for the mechanism of the accumulation, a metabolic inhibition experiment showed that the accumulation is not due to increased influx of the drug into the cells but due to an azelastine-effected decrease in the efflux of the drug from the cells. Thus, the effect of azelastine on the binding of P-glycoprotein in plasma membrane fraction with VCR was examined.[3H] VCR binding to the membrane fraction prepared from an ADM-resistant human myelogenous leukemia cell line (K562/ADM) was inhibited by azelastine in a concentration-dependent manner. These results imply that azelastine circumvents multidrug resistance through, at least partly, the inhibition of the efflux of anti-cancer drug from leukemia cells by its binding to P-glycoprotein. We further noted that the treatment with azelastine in combination with VCR significantly prolonged the survival of P388/VCR-bearing mice as compared with those given VCR alone.

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Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: Implications for its mode of action

Cited by 123 publications

References 8 publications

Inhibition of allergic and non‐allergic histamine secretion from rat peritoneal mast cells by calcium antagonists

Inhibition of allergic and non‐allergic histamine secretion from rat peritoneal mast cells by calcium antagonists

Modulation of in vitro anaphylaxis of guinea‐pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs

Circumvention of Multidrug Resistance of Leukemia Cells by the Anti-Allergic Agent Azelastine.

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