The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology.

Tbiological activity of one major class of leukotrienes, originally described as slow reacting substance of anaphylaxis (SRS-A)' (1, 2) and now known to be composed of the sulfidopeptide leukotrienes, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-I 1, 14-cis-eicosatetraenoic acid (leukotriene C4, LTC4), 5S-hydroxy-6R-S-cysteinylglycyl-7,9-trans-11, 14-cis-eicosa- tetraenoic acid (leukotriene D4, LTD4), and 5S-hydroxy-6R-Scysteinyl-7,9-trans-1 1, 14-cis-eicosatetraenoic acid (leukotriene E4, LTE4) (3-7), has been known for over 40 years. The biological activity and structure of the second major class of leukotrienes, represented solely by 5S-12R-dihydroxy-6,14-cis-8, I0-trans- eicosatetraenoic acid (leukotriene B4, LTB4), was recognized only 5 years ago On the basis of the earlier definition of SRS-A in terms ofchromatographic, functional, and chemical characteristics (12-15), it was possible to generate a similar material with radiolabeled constituents by ionophore activation of mouse mastocytoma cells and to achieve a chemical characterization of LTC4 (3). The stereospecific synthesis of both LTC4 (16) and LTB4 ( . Abbreviations used in this paper: 5-HPETE, 5S-hydroperoxy-6-trans-8,1 1,14-cis-eicosatetraenoic acid; LTA4, 5,6-trans-oxido-7,9-trans-1 1,14cis-eicosatetraenoic acid; LTB4, 5S-12R-dihydroxy-6,14-cis-8, 10-transeicosatetraenoic acid; LTC4, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-1 1,14-cis-eicosatetraenoic acid; LTD4, 5S-hydroxy-6R-S-cysteinylglycyl- 7,9-trans-I 1,14-cis-eicosatetraenoic acid; LTE4, 5S