A FAMILY OF CALCIUM IONOPHORE-INDUCED SLOW REACTING SUBSTANCES PRODUCED BY RAT MONONUCLEAR-CELLS - ENHANCEMENT OF PRODUCTION WITH DIFFERENT MERCAPTANS RESULTS IN FORMATION OF DIFFERENT PRODUCTS

Slow reacting substances are produced when mononuclear cells, which were isolated from the peritoneal cavity of thioglycolate-stimulated rats, are incubated with the calcium ionophore, A 23187. Production of such slow reacting substances can be markedly enhanced if relatively high concentrations of various mercaptocarboxylic acids are added to the cells a few minutes before addition of the ionophore. Using high performance liquid chromatography, each of these preparations could be resolved into two fractions, both of which qualitatively satisfied the criteria for characterization as slow reacting substance of anaphylaxis. However, based on differences in mobility during chromatography, as well as differences in susceptibility to inactivation by acid, alkali, and by incubation with aryl sulfatase, it appears that different reaction products are formed when different mercaptans are used in the incubation. These results expand our previously published finding that slow reacting substance which was generated with rat mononuclear cells can be resolved into two biologically active fractions. They point to the existence of a whole family of slow reacting substances which differ structurally as a function of the mercaptocarboxylic acid which was used to potentiate their formation. Thus they suggest the possibility that major portions of the atomic skeleton of the mercaptocarboxylic acids may be incorporated into the structure of the slow reacting substances which are formed. This finding offers an explanation for the mechanism of action of the mercaptocarboxylic acids in the stimulation of slow reacting substance formation and perhaps gives a hint in the quest for the elucidation of the structure of slow reacting substance of anaphylaxis. © 1979.