Inhibition by Cromoglycate of Histamine Release From Rat Peritoneal Mast Cells Induced by Mixtures of Dextran, Phosphatidyl Serine and Calcium Ions

Abstract

1Dextran releases histamine from rat peritoneal mast cells in the presence but not in the absence of phosphatidyl serine (PS). With PS (10 ,g/ml) present the effect of dextran was concentration-dependent in the range of 0.2-6 mg/ml. 2 PS releases little histamine on its own but mixed with dextran (6 mg/ml) produces a graded effect in the range of 0.3-10 Mg/ml.3 The combination of dextran and PS releases no histamine in a medium containing less than 0.1 mm calcium. As the calcium concentration is increased, release occurs and a maximum is reached at calcium 1 mM; at higher concentrations release falls off sharply.4 Histamine release by the combination of dextran (6 mg/ml), PS (10 mg/ml) and calcium (1.8 mM) is inhibited by cromoglycate in the same range (1-30 gM) that inhibits anaphylactic histamine release from rat peritoneal cells. 5 Inhibition by cromoglycate occurred with all dextran concentrations tested (0.2-15 mg/ml) but high concentrations of PS (30 and 100 Mg/ml) overcame the effect of cromoglycate (2 and 10 uM). Calcium concentrations above 1 mM augmented inhibition by cromoglycate 2 and 10 AM.

The Relationship Between Energy Metabolism and the Action of Inhibitors of Histamine Release

“…Histamine release was induced by dextran from mixed peritoneal cells of male Wistar rats (1-5% mast cells) prepared in vitro as described previously (Garland & Mongar, 1974). A 0.5 ml volume of a mixture of dextran and phosphatidyl serine (PS) was added to 0.5 ml cells preincubated for 30 min at 370C in Tyrode solution with or without glucose (5.6 mmol/l); the final concentrations were dextran 6 mg/ml, PS 30 gg/ml.…”

“…1971), desensitization and cross-desensitization with antigen (Foreman & Garland, 1974;Foreman, Garland & Mongar, 1976) and inhibition by antiallergic agents such as cromoglycate (Garland & Mongar, 1974). Furthermore, the reaction is diminished by metabolic inhibitors such as 2,4-dinitrophenol (Beraldo, Dias da Silva & Lemos Fernandes, 1962).…”

Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels.

“…If glucose was included with antimycin A (10-6 M) and deoxyglucose removed, the secretary response to neurotensin was restored (19-8±1)%I n= 3). Cromoglycate has been shown to inhibit histamine release from rat mast cells stimulated by a variety ofsecretagogues including antigen (Garland, 1973), compound 48/80 (Orr, Hall, Gwillian, & Cox, 1971;Spataro & Bosmann, 1976), dextran (Garland & Mongar, 1974) or ionophore A23187 (Johnson & Bach, 1975 …”

Disodium cromoglycate inhibition of substance P-induced histamine secretion is calcium dependent.

“…It effectively inhibits histamine release (secretion) from rat peritoneal mast cells as induced by the binding of a specific antigen to cell-bound IgE antibody (3)(4)(5) as well as by a variety of chemical substances such as dextran (5), compound 48/80 (3,(6)(7)(8), substance P (8) and neurotensin (8). Possible mechanisms of the action of DSCG include: blocking of the influx of Ca 21 into mast cells (6,9), in hibition of phosphodiesterase (10, 11) and regulation of phosphorylation of mast cell protein (12).…”