Effect of Nedocromil Sodium on the Compound Exocytosis of Mast Cells

Abstract

The secretory activity of peritoneal mast cells was studied in vitro after challenge with compound 48/80 of cells obtained from normal rats and with anti-rat IgE of cells obtained from rats hyperimmunised with Nippostrongylus brasiliensis. Peritoneal mast cells were isolated from 2 groups of rats aged 2 to 3 months and 5 to 6 months. After purification, the cells were preincubated with or without nedocromil sodium for 5 minutes followed by addition of secretagogue and incubation for an additional period of 5 minutes (compound 48/80) or 15 minutes (anti-IgE). The secretory response was analysed by measurement of the release of endogenous histamine and serotonin (5-hydroxytryptamine) into the medium using high performance liquid chromatography, and by the assay of the heparin content of individual mast cells by cytofluorometry, using the fluorescent dye berberine as a quantitative marker. Concentrations of secretagogues which gave 30 to 40% amine release in controls without inhibitor were selected. In agreement with previous reports, the degree of release of histamine was slightly higher than that of serotonin, but nedocromil sodium suppressed the release of both amines in a parallel manner, without any differential effect, after stimulation with both compound 48/80 and anti-IgE. The effect of nedocromil sodium was concentration-dependent, with the lowest effective concentration in the range of 10(-8) to 10(-7) mol/L, and reduced release to about 40% of control values. Mast cells from young rats responded with a significantly higher amine release than mast cells from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)