Comparative biological activities of the four synthetic (5,6)-dihete isomers.

(5,6)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids ((5,6)-DiHETEs) were synthesized and separated into four pure diastereoisomers. They were tested for comparative binding affinities to leukotriene receptors (LTC4, LTD4, LTB4) in guinea pig ling membranes. Only (5S,6R)-DiHETE was recognized by the LTD4 receptor, the other receptors interacted with neither of the four isomers. (5S,6R)-DiHETE also contracted ileum in vitro and this effect was inihibited by the LTD4 receptor antagonists ICI 198,615 and SKF104,353. These data suggest that the biproduct (5S,6R)-DiHETE generated by enzymatic conversion of LTA4 could have some LTD4-like activity when produced in large concentrations.