The biotransformation in vitro of cysteinyl leukotrienes in blood of normal and asthmatic subjects.
The metabolism of exogenous leukotriene C4 (LTC4), LTD4 and LTE4 (10(-8) M) was studied in vitro in blood of normal and asthmatic subjects for up to 2 hr by reverse-phase high performance liquid chromatography. In whole blood, incubation of LTC4 (T1/2 = 11.5 min) resulted in the formation of LTD4 and LTE4 whose biosynthesis was inhibited by serine borate (30 mM). Similar experiments performed with LTD4 (T1/2 = 5 min) produced a single metabolite (LTE4) which was inhibited by L-cysteine (10 mM). On the other hand, LTE4 represented a highly stable product in our in vitro system. The bioconversion of LTC4 or LTD4 was slower in plasma but this effect appeared more pronounced for the cysteinylglycinyl derivative. The bioconversion of LTD4 in whole blood or plasma was almost twice as rapid as LTC4. Experiments performed with asthmatic blood showed no significant difference in the survival of LTC4. These results suggest that blood may play a role in regulating the bioavailability of cysteinyl-containing LTs which could be of relevance to their excretion in man.
Zakrzewski
J T
JT
Dept. of Thoracic Medicine, King's College School of Medicine and Dentistry, Denmark Hill, London.
Sampson
A P
AP
Evans
J M
JM
Barnes
N C
NC
Piper
P J
PJ
Costello
J F
JF
D000328:Adult; D001249:Asthma / Q000097:blood*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007700:Kinetics; D017999:Leukotriene E4; D008297:Male; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D013189:SRS-A / Q000031:analogs & derivatives* / Q000097:blood*; D014316:Tritium
D013189:SRS-A; D014316:Tritium; D017999:Leukotriene E4