Two rat mononuclear cell-derived slow reacting substances: kinetic evidence that the peripheral airways-selective...

The purpose of this study was to extend our knowledge of two slow reacting substances that are formed in rat mononuclear cells upon stimulation by the ionophore A 23187. Slow reacting substance (SRS) preparations were further purified through the sequential high performance liquid chromatographic procedures starting with exudates from cells that had been prelabeled with tritiated arachidonate. Approximately 2% of the released radioactivity (0.3% of the radioactivity that was taken up by the cells) cochromatographed with biologic activity in both preparations. Kinetic studies revealed that one of the SRSs was formed more rapidly than the other and analysis by nonlinear computer modeling techniques suggests a possible product-precursor relationship between the two substances. Activity of the preparations on guinea pig lung parenchyma and trachea was compared using a histamine standard; only the more slowly formed substance had the selective activity on the parenchyma that we associate with slow reacting substance of anaphylaxis (SRS-A). Taken together, these findings suggest that a material which may be a precursor of SRS-A, if it is also formed and accumulated in vivo, may contribute to the more central airway constriction which is seen in some asthmatics.