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L Orning

Publications and source records attributed to L Orning.

46 records · Page 3Linked to original sources

Characteristics of the uptake of cysteine-containing leukotrienes by isolated hepatocytes.

Leukotrienes were transported into rat hepatocytes by a temperature- and energy-dependent mechanism. The uptake was saturable with high- and low-affinity sites (Km values approx. 1 and 17 microM). Competition and kinetic experiments indicated that leukotrienes C4, D4 and E4 were transported by a common mechanism. The maximal velocity of transport was about 50% higher for leukotrienes D4 and E4 than for leukotriene C4. Leukotriene B4, glutathione disulfide, and the glutathione-S-conjugate of acetaminophen did not interfere with the transport of leukotriene C into hepatocytes. This suggests that the process is specific for cysteine-containing leukotrienes. It is likely that the transport mechanism described here participates in biliary excretion of leukotrienes. This route was previously found to be a major one for elimination of leukotriene C3 in mice and guinea-pigs.

Acetaminophen↗

Isolation and characterization of 15-hydroxylated metabolites of leukotriene C4.

A polar metabolite of leukotriene C4 was formed by sequential conversions with soybean lipoxygenase I and liver peroxidase. The structure of this product was found to be 5(S), 15(S)-dihydroxy-6(R)-S-glutathionyl-7,9,13-trans-11-cis-eicosatetraenoic acid (15-hydroxy-delta 13-trans-leukotriene C3. The HPLC behaviour, the molar extinction coefficient and the biological activity of the metabolite are reported. Preliminary evidence suggests that this product is formed by mammalian tissues.

Animals↗

Formation of leukotrienes E3, E4 and E5 in rat basophilic leukemia cells.

Rat basophilic leukemia (RBL-1) cells incubated with ionophore A23187 and 5,8,11-eicosatrienoic acid produced three slow-reacting substances identified as leukotrienes C3, D3 and E3 by spectroscopic, chromatographic and enzymatic methods. 5,8,11,14,17-Eicosapentaenoic acid was similarly converted by RBL-1 cells to leukotrienes C5, D5. and E5. Leukotrienes C4, D4 and E4 were also formed in these experiments from endogenous arachidonic acid. Time-course studies, incubations with 3H-labeled leukotriene C3 and effects of acivicin [L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; a gamma-glutamyl transpeptidase inhibitor] indicated that leukotrienes C and D are intermediates in the formation of leukotrienes E. L-Cysteine enhanced the conversion of leukotriene C3 to leukotriene D3 and inhibited further degradation of leukotriene D3 to leukotriene E3.

8,11,14-Eicosatrienoic Acid↗

Inhibition of leukotriene C and leukotriene D biosynthesis.

Leukotriene C4 and leukotriene D4 are slow reacting substances produced by mouse mastocytoma cells and rat basophilic leukemia cells, respectively. Serine x borate complex, an inhibitor of glutamyl transpeptidase (EC 2.3.2.2), prevented the formation of the biologically more potent leukotriene D4 and caused accumulation of leukotriene C4 in rat basophilic leukemia cell suspensions. 5,8,11-Eicosatriynoic acid, a lipoxygenase inhibitor, prevented the biosynthesis of leukotriene C4 (ID50, 5 microM) by mastocytoma cells. The results demonstrate that gamma-glutamyl transpeptidase is involved in the biosynthesis of leukotriene D4 and suggest that leukotriene C4 is formed as an intermediate.

Animals↗

Leukotriene D: a slow reacting substance from rat basophilic leukemia cells.

A slow reacting substance produced by rat basophilic leukemia cells, treated with ionophore A23187, was characterized by spectroscopic methods, enzymatic conversions, and chemical degradations as 5-hydroxy-6-S-cysteinylglycyl 7,9,11,14-eicosatetraenoic acid (leukotriene D). gamma-Glutamyltranspeptidase [gamma-glutamyltransferase; (5-glutamyl)-peptide: amino-acid 5-glutamyltransferase, EC 2.3.2.2] converted leukotriene C to a product identical to leukotriene D. This suggests that the stereochemistry of the arachidonyl moiety of leukotrienes C and D is the same [5(S)-6(R)-7,9-trans-11,14-cis]. Leukotriene D induces a faster contraction and, on a molar basis, is more potent than leukotriene C in the isolated guinea pig ileum bioassay.

Amino Acids↗