The biotransformation in vitro of cysteinyl leukotrienes in blood of normal and asthmatic subjects

Zakrzewski, J. T., Sampson, A. P., Evans, J. M., Barnes, N. C., Piper, P. J. and Costello, J. F. (1989) The biotransformation in vitro of cysteinyl leukotrienes in blood of normal and asthmatic subjects. Prostaglandins, 37 (4), 425-444. (doi:10.1016/0090-6980(89)90093-2).

Abstract

The metabolism of exogenous leukotriene C₄ (LTC₄), LTD₄ and LTE₄ (10^-8M) 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 (T _{1 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 (T _{1 2} = 5 min) produced a single metabolite (LTE₄) which was inhibited by L-cysteine (10mM). 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 LTC₄ in 4 whole blood or plasma was almost twice as rapid as LTC₄. Experiments performed with asthmitic 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.

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Contributors

Author: A. P. Sampson

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