Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources

Abstract

Slow reacting substance(s) of anaphylaxis (SRS-A) was isolated from both human (lung) and rat sources and compared with three synthetic SRS-As of known structure—leukotrienes (LTs) C-1, C-2, and D. Reversed-phase liquid chromatography was used both as a final purification step and a means of comparison of biologically derived and synthetic substances. Two major peaks of SRS-A activity of both rat and human origin corresponded chromatographically with LTC-1 and LTD, respectively, and had equivalent specific activities on the guinea pig ileum. With guinea pig ileum, the specific activities (units/pmol) for synthetic leukotrienes and anaphylactic peaks were (mean ± SEM): synthetic LTC-1, 1.93 ± 0.13; SRS-A^rat peak I, 1.69 ± 0.43; synthetic LTD, 6.10 ± 1.15; SRS-A^rat peak II, 7.14 ± 0.51; and SRS-A^hu peak II, 1.90. Both synthetic LTC-1 and LTD and their SRS-A natural counterparts had a preferential contractile activity on guinea pig peripheral airway compared to central airways and were at least 200 times more active than histamine on peripheral airways on a molar basis. Leukotriene D is the major SRS-A of human lung and accounts for almost all of the biological activity. It likely is formed from leukotriene C-1 in vivo by an enzymic process of the well-known γ-glutamyltransferase type.