Interaction of Disodium Cromoglycate with Calcium Ions in 2-Propanol

Spitzer, J.C.

doi:10.1159/000232361

Cited by 10 publications

(6 citation statements)

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“…The disodium salt of 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane, cromolyn, inhibits Ca2+ uptake and hence the release of anaphylactic mediators from mast cells and has found wide application in the prophylactic treatment of allergic bronchial asthma (6)(7)(8)(9). The drug has been shown to chelate alkaline earth ions in low polarity medium with a clear preference of Ca2+ over Mg2' (10,11). Moreover, a specific Ca2+-dependent binding site, through which the pharmacological behavior of cromolyn is expressed, has been demonstrated on the surface membrane of mast cells and RBL-2H3 cells (12).…”

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confidence: 99%

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Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Mazurek¹,

Bashkin

Loyter

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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Recently, variants of the rat basophilic leukemia cells (RBL-2H3), deficient in their binding capacity for the antiallergic drug cromolyn but displaying unimpaired ability to bind IgE, were selected and cloned [Mazurek, N., Bashkin, P., Petrank, A. & Pecht, I. (1983) Nature ( London ) 303, 528-530]. Although the histamine content and the number of IgE receptors in these variants are similar to those of the parental cells, they cannot be stimulated immunologically to allow Ca 2+ influx and to degranulate. In contrast, the Ca 2+ ionophore A23187 causes these variants to degranulate, indicating that the mechanism distal to the Ca 2+ gating is intact in the variants. The cromolyn binding protein (CBP), present in the membranes of RBL-2H3 cells, has recently been isolated by affinity chromatography under nondenaturing conditions. In the current study we have used Sendaivirus envelopes as fusogenic carriers to implant the purified CBP into the membrane of variant basophils that were defective in it. This fusion leads to the restoration of Ca 2+ uptake and degranulation capacity of the variants after IgE-mediated stimulation. These restored activities seem to show a sigmoidal dependence on the amount of incorporated CBP. Saturation values comparable to those of the parental line are reached when the level of implanted CBP approaches its density on the latter line. The restored capacity is due to the implanted CBP, because the reinstated immunological response can be blocked by the inhibitory drug cromolyn and by monoclonal antibodies specific to CBP, both shown to prevent Ca 2+ uptake and degranulation in mast cells and parental RBL-2H3 cells. These results point out that CBP plays an important role in the Ca 2+ gating process resulting in degranulation.

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“…Sci. USA 80 (1983) 6017 10 Ci/mol) was added 10 min prior to the challenge with (DNP)8 BS albumin for 30 min at 370C. The supernatant was sampled for degranulation and the cells were assayed for calcium uptake.…”

mentioning

confidence: 99%

Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Mazurek¹,

Bashkin

Loyter

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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“…"0' Confluent cells in T-75 flasks were detached by trypsinization (0.12% for 5-7 minutes) and were treated with appropriate amounts of trypsin inhibitor (soybean). Cells were plated in 96-well flat-bottom microtiter well plates (25,000 cells/well) in medium M199 containing 10% (vol/vol) FBS. Approximately 72 hours later, confluent cells were incubated with fresh medium containing 0.4% FBS.…”

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confidence: 99%

Inflammatory Mediators in Airway Muscle Proliferation

Tran¹,

Weil²

1992

Pediatric Asthma, Allergy & Immunology

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Chronic severe asthma is characterized by airway smooth muscle hypertrophy-hyperplasia that may be intricately related to chronic airway hyperreactivity. We conducted studies to examine the mitogenic effects of inflammatory mediators on airway smooth muscle in reference to known growth factors of smooth muscle. Potential therapeutic agents for airway smooth muscle proliferation were tested in bovine trachéal myocyte tissue culture system. ß-Hexosaminidase (50 nM) caused an increase in 3H-thymidine incorporation in confluent cells comparable to the effect of the optimum concentration of insulin (5 µ, ) and tumor necrosis factor alpha (6 nM). The mitogenic effect of Hex was superior in magnitude to that of the optimum concentration of histamine (100 µ ), platelet-derived growth factor (0.14 nM), insulinlike growth factor-II (10 nM), and transforming growth factor alpha 14 (nM). Hex B-induced mitogenic effect was significantly inhibited by disodium cromoglycate (DSCG, 10-20 mM) but not by either cyclooxygenase inhibitor indomethacin (10 µ, ) or 5-lipoxygen¬ ase inhibitor AA861 (1 µ ). We conclude that inflammatory mediators implicated in asthma (Hex B, histamine) contribute to airway smooth muscle proliferation. The results of this study also suggest that DSCG has a novel antimitogenic function in airway smooth muscle.

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“…Figure 1 shows that histamine release from isolated peritoneal mast cells of R rats by all three agents (BSA, Con A and dex tran) was greatly enhanced when PS was present and was inhibited when disodium cromoglycate (DSCG, 10 //g m l'1) was in cluded in the incubation mixture. PS and DSCG may compete for the same factor in volved in histamine release [6], For exam ple, two molecules of PS can combine with one of calcium, and DSCG in an organic medium containing traces of water can com plex with calcium ions [7]. So, PS and DSCG may compete for the available cal cium.…”

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Histamine Release from Isolated and Intact Mast Cells of Rats

Gb¹

1981

Int Arch Allergy Immunol

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The release of histamine from tissues of rats, induced by antigen, concanavalin A and dextran has been compared with that from isolated peritoneal mast cells. Whereas concanavalin A was more active than dextran in in vitro experiments, the reverse was found when the substances were injected intradermally into the skin or subcutaneously into the paw. Therefore, it is important to state the experimental conditions when comparisons of activities of histamine releasers are made.

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Interaction of Disodium Cromoglycate with Calcium Ions in 2-Propanol

Abstract: Spectral evidence is presented which indicates that calcium ions can complex with the cromoglycate anion in an organic medium containing a small amount of water. The implications of this finding for the antiasthmatic activity of disodium cromoglycate are discussed.

Cited by 10 publications

References 4 publications

Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Inflammatory Mediators in Airway Muscle Proliferation

Histamine Release from Isolated and Intact Mast Cells of Rats

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Interaction of Disodium Cromoglycate with Calcium Ions in 2-Propanol

Abstract: Spectral evidence is presented which indicates that calcium ions can complex with the cromoglycate anion in an organic medium containing a small amount of water. The implications of this finding for the antiasthmatic activity of disodium cromoglycate are discussed.

Cited by 10 publications

References 4 publications

Restoration of Ca 2+ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Restoration of Ca 2+ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Inflammatory Mediators in Airway Muscle Proliferation

Histamine Release from Isolated and Intact Mast Cells of Rats

Contact Info

Product

Resources

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Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein

Restoration of Ca ²⁺ influx and degranulation capacity of variant RBL-2H3 cells upon implantation of isolated cromolyn binding protein