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In Vivo and in Vitro Production of a Slow Reacting Substance in the Rat Upon Treatment with Calcium Ionophores

Department of Hypersensitivity Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001

Abstract

Injection of the divalent metal ion-specific ionophores, A 23187 and X 537A, into the peritoneal cavity of the rat resulted in the release of histamine. In addition, there was produced a large amount of a substance which caused slow contractions of the atropinized, mepyramine-treated guinea pig ileum. A similar activity was also produced when mixed peritoneal cells were incubated with the ionophores in vitro in the presence of physiologic buffer solutions containing calcium ions. Production of the activity in vivo was unaffected by pretreatments of the animals to deplete them of mast cells, polymorphonuclear neutrophils, or both, or by the depletion of complement activity with cobra venom factor. The activity was stable to alkali and to incubation with chymotrypsin. Chromatography on XAD-2 resin followed by partition chromatography on silicic acid resulted in the recovery of the activity in an ethanolic ammonia eluate. These chemical characteristics and the yield of the recovered activity are reminiscent of the behavior of slow reacting substance of anaphylaxis (SRS-A) under the same conditions.