Structure elucidation and biosynthesis of slow reacting substances and slow reacting substance of anaphylaxis from guinea pig and human lungs

Abstract

The structure of slow reacting substance of anaphylaxis (SRS-A) from lung is defined by advanced spectroscopic and protein chemical methods to be 5-hydroxy-6-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid, CYS-GLY SRS-A. 12SRS-A is identical to the major SRS released non-immunologically from rat basophil leukaemia (RBL-1) cells whose structure we first defined as the dipeptidyl (CYS-GLY) peptidolipid. 9 Human lung SRS-A is chromatographically indistinguishable from guinea-pig lung SRS-A, suggesting that this is also the CYS-GLY SRS-A structure. 7 SRS-A is biosynthesized by a combination of lipoxygenase metabolism of arachidonic acid 8,15 coupled with the glutathione detoxification pathway. Glutathione S- transferase and γ-glutamyl transferase levels in both the lung and isolated cell systems have been measured before, during and after immunological and non-immunological challenge. Enzyme levels rise significantly upon challenge and coincide with the release of SRS-A and SRS.