Comparison of urinary leukotriene E4 and 16-carboxytetranordihydro leukotriene E4 excretion in allergic asthmatics after inhaled antigen.
Antisera to 16-carboxytetranordihydro leukotriene E4 (tetranor LTE4), a major urinary oxidative metabolite (via omega- and beta-oxidation) of leukotriene E4 (LTE4) in primates, were obtained by immunisation of rabbits with a related, non-naturally occurring synthetic metabolite (16-carboxytetranordihydro leukotriene C4 ester) conjugated to Keyhole Limpit haemocyanin. Material which competed with [11, 12-3H]tetranor LTE4 for binding to this antisera was isolated from urine from allergic asthmatics by reversed-phase HPLC. This material eluted with the retention time of synthetic standards, and its mean urinary excretion was elevated during both the first three hours (6.13 +/- 2.15 ng/h) and 3-6 h (5.87 +/- 1.99 ng/h) after antigen inhalation, compared with baseline values (3.42 +/- 1.49 ng/h), in 5 allergic mild asthmatics. A much greater and statistically significant increase in urinary leukotriene E4 (LTE4) excretion, occurring in all subjects, was seen during acute antigen-induced bronchoconstriction (baseline, 1.62 +/- 0.66 ng/h; 0-3 h, 19.58 +/- 8.79 ng/h; p less than 0.05) in these subjects. These data support the suggestion that endogenous peptide leukotrienes are metabolised by omega- and subsequent beta-oxidation in man, but emphasize the relative importance of urinary LTE4 excretion after allergen elicited leukotriene generation, further substantiating a pathological role for peptide leukotrienes in allergic asthma.
Tagari
P
P
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Rasmussen
J B
JB
Delorme
D
D
Girard
Y
Y
Eriksson
L O
LO
Charleson
S
S
Ford-Hutchinson
A W
AW
D000281:Administration, Intranasal; D000328:Adult; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D017999:Leukotriene E4; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine
D000941:Antigens; D013189:SRS-A; C066047:16-carboxytetranordihyroleukotriene E4; D017999:Leukotriene E4