Identification and biological activity of dihydroleukotriene B4: a prominent metabolite of leukotriene B4 in the human lung.
Exogenous [3H]leukotriene B4 (LTB4) was converted into several polar and non-polar metabolites in the chopped human lung. One of the major metabolites was identified as 5(S),12-dihydroxy-6,8,14-eicosatrienoic acid (10,11-dihydro-LTB4) by means of co-chromatography with authentic standards, ultraviolet spectrometry and gas chromatography-mass spectrometry. Analysis of chiral straight phase HPLC revealed the presence of both the 12(S) and 12(R) epimers of dihydro-LTB4. Dihydro-LTB4 was also formed from endogenously generated LTB4 in ionophore A23187 stimulated incubations. The dihydro metabolites were approximately 100 times less potent than LTB4 in causing guinea pig lung strip contraction and leukocyte-dependent inflammation in the hamster cheek pouch in vivo.
Kumlin
M
M
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Falck
J R
JR
Raud
J
J
Harada
Y
Y
Dahlén
S E
SE
Granström
E
E
D000818:Animals; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007975:Leukotriene B4 / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology / Q000031:analogs & derivatives; D008168:Lung / Q000187:drug effects / Q000378:metabolism*
C064945:5,12-dihydroxy-6,8,14-eicosatrienoic acid; D007975:Leukotriene B4