Abstract
[5,6,8,9,11,12-3H6]Leukotriene C3 was converted to polar metabolites which ere excreted in feces and urine for 4-5 days after subcutaneous administration to guinea pigs. Lung homogenates converted leukotriene C3 to leukotriene D3. Liver and kidney homogenates did not catabolize leukotriene C3 appreciably due to inhibition of gamma-glutamyl transpeptidase in these tissues by endogenous glutathione. Liver and kidney homogenates metabolized [3H6]leukotriene D3 to the cysteine analog, leukotriene E3 (Bernström, K., and Hammarström, S. (1981) J. Biol. Chem. 256, 9579-9582). In addition leukotriene C3 and products of greater polarity were formed. The conversion of leukotriene D3 to leukotriene C3 was catalyzed by gamma-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 D3 is important for the further metabolism of this leukotriene in liver and kidney.
Highlights
From theDepartment of Chemistry, Karolinska Znstitutet, S-10401 Stockholm, Sweden [6,6,8,9,11,12-3He]leukotrieneC3was converted to por-everse phase HPLC' [8]was 1.5 mCi and thespecific activity was 50 lar metabolites which were excreted in faencdesurine Ci/mmol based on radioactivity and UV absorbance measurements
To prepare tritium-labeled leukotriene D3, 10 pCi of [3&]leukotriene C3 was treated with 0.2 mg/ml of partiaUy purified porcine kidney y-glutamyl transpeptidase (Sigma) in 0.05 ml bition of y-glutamyl transpeptidasein these tissuesby of 0.1 M T&.HC1/0.01 M MgCh, pH 8.5, at 37 "C for 30 min
The results sug- rately. gest that the degradation of leukotriene C3 to leuko- After the collecting period, the specimens were stored frozen at -20 triene Ds is important for the further metabolism of OC
Summary
From theDepartment of Chemistry, Karolinska Znstitutet, S-10401 Stockholm, Sweden [6,6,8,9,11,12-3He]leukotrieneC3was converted to por-everse phase HPLC' [8]was 1.5 mCi and thespecific activity was 50 lar metabolites which were excreted in faencdesurine Ci/mmol based on radioactivity and UV absorbance measurements. Gest that the degradation of leukotriene C3 to leuko- After the collecting period, the specimens were stored frozen at -20 triene Ds is important for the further metabolism of OC 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-containingdeweighed, and minced with a pair of scissors in 4 volumes of cold 20 n m KHzP04/72 n m K*HP0&3 mM nicotinamide/3.6 m~ MgC12, pH 7.4 [11].The suspensions were homogenized (Potter-Elvehjem type) and centrifuged a t 950 X g for 15 min. HPLC-Unless otherwise stated, the column (500X 10 m m ) concutaneous administration and itscatabolism by cell-freeprep- tained CIS Polygosil(5pm; Machery-Nagel) andthe solvent was arations of lung, liver, and kidney of the guinea pig.
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