Leukotriene C: A slow-reacting substance fro urine mastocytoma cells

Murine mastocytoma cells ated with um ionophore A.23187 prod a slow-reacting substan (SRS) that caused guinea pig ileum to contract. The response was reversed by the SRS antagonist 12. On the basis of isotope incorporation experiments, spectroscopy, and chemical degra" dation% the SRS was identified as a cysteine-containing derivative of 5"hydroxy-7,9,11,14-icosatetraenoie acid. This amino acid was attached in thioether linkage at C-6. The SRS is structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. A common feature is the presence of a conjugated triene, and the name "leakotrienc" has been introduced to designate these compounds. Leukotriene A (5,6-epoxy-7,9,11,14-icosatetraenoic acid) is an intermediate in the formation of leukotriene B (5,12-dihr droxy-6,8,10,14-icosatetraenoic acid) and is proposed to be a precursor also of leukotriene C, which is the SRS identified here.