Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver, and kidney.
1981; Elsevier BV; Volume: 256; Issue: 18 Linguagem: Inglês
10.1016/s0021-9258(19)68800-9
ISSN1083-351X
Autores Tópico(s)Vitamin K Research Studies
Resumo6,6,8,9,11,]leukotriene C3 was converted to polar metabolites which were excreted in feces and urine for 4-6 days after subcutaneous administration to guinea pigs.Lung homogenates converted leukotriene C3 to leukotriene Da.Liver and kidney homogenates did not catabolize leukotriene Cs appreciably due to inhibition of y-glutamyl transpeptidase in these tissues by endogenous glutathione.Liver and kidney homogenates metabolized ['He]leukotiene D 3 to the cysteine analog, leukotriene E3 (Bernstrom, K., and Hammarstrom, S. (1981) J. BioL Chem.266, 9679-9682).In addition leukotriene C a and products of greater polarity were formed.The conversion of leukotriene Ds to leukotiene C3 was catalyzed by y-glutamyl transpeptidase which performed a reverse reaction due to the high tissue concentrations of glutathione.The results suggest that the degradation of leukotriene C3 to leukotriene Ds is important for the further metabolism of this leukotriene in liver and kidney.Slow reacting substance of anaphylaxis (SRS-A) is a smooth muscle contracting factor presumed to be a mediator of allergic symptoms, e.g. in asthma (reviewed in Ref. l).Although SRS-A was first described in 1938 (2) its structure was elucidated only recently (3, 4).The parent compound is a novel derivative of arachidonic acid containing a glutathione substituent.It has been designated leukotriene C4 (5).Leukotriene D4, the corresponding cysteinylglycine-containing derivative of arachidonic acid, has also been identified (6, 7).In addition, leukotrienes having different numbers of double bonds (leukotrienes C3, D3 (8), CS, and Ds (9,lO)) have been characterized.Tritium-labeled leukotriene C3 of high specific activity was recently prepared biosynthetically from [5,6,8,9,11,12-3H~]5,8,11-eicosatrienoic acid (8).The present report deals with the excretion of this compound after subcutaneous administration and its catabolism by cell-free preparations of lung, liver, and kidney of the guinea pig.,6,8,9,11,12-3H~Leukoh.ienes C3 and W-These compounds were prepared as described before (8).[5,6,8,9,11,12-3&]5,8,11-Ei~~~atrienoic acid (0.1 Ci; 62 Ci/mmol) was incubated with 7. log mastocytoma cells in the presence of lo-' M cysteine and 20 p~ A23187 for 20 min at 37 "C.The yield of tritium-labeled leukotriene C3 after chromatographic purification on Amberlite XAD-8, silicic acid, and MATERIALS AND METHODS ~5
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