Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources.
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 gamma-glutamyltransferase type.
D000818:Animals; D012898:Autacoids / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology
D012898:Autacoids; D013189:SRS-A; C025492:leukotriene C-2