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

TLDR

Leukotriene D is formed from leukotriene C‑1 in vivo via a γ‑glutamyltransferase–mediated enzymatic process. The authors isolated slow‑reacting substance(s) of anaphylaxis from human lung and rat tissues and compared them to synthetic leukotrienes C‑1, C‑2, and D using reversed‑phase liquid chromatography for purification and comparative analysis. Both natural and synthetic LTC‑1 and LTD showed potent contractile activity on guinea pig peripheral airways, with LTD being the major SRS‑A in human lung and accounting for almost all biological activity, and specific activities ranging from 1.69 to 7.14 units/pmol, indicating comparable potency between natural and synthetic compounds.

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.