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 lung 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 inhibited by the LTD4 receptor antagonists ICI 198,615 and SKF104,353. These data suggest that the bioproduct (5S,6R)-DiHETE generated by enzymatic conversion of LTA4 could have some LTD4-like activity when produced in large concentrations.
Muller
A
A
Laboratoire de Physiologie Cellulaire, Faculté de Pharmacie, Université Montpellier I, France.
Rechencq
E
E
Kugel
C
C
Lellouche
J P
JP
Beaucourt
J P
JP
Niel
G
G
Girard
J P
JP
Rossi
J C
JC
Bonne
C
C
D000818:Animals; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000502:physiology; D007082:Ileum / Q000187:drug effects; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D013237:Stereoisomerism
D006893:Hydroxyeicosatetraenoic Acids; C048698:5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid