Identification of the major endogenous leukotriene metabolite in the bile of rats as N-acetyl leukotriene E4

Journal Article · Sat Feb 01 04:00:00 EST 1986 · Prostaglandins; (United States)

DOI:https://doi.org/10.1016/0090-6980(86)90050-X· OSTI ID:5531846

Hagmann, W; Denzlinger, C; Rapp, S; Weckbecker, G; Keppler, D

Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats in vivo after endotoxin treatment. The mercapturate N-acetyl-leukotriene E4 (N-acetyl-LTE4) represented a major metabolite eliminated into bile after injection of (/sup 3/H)LTC4 as shown by cochromatography with synthetic N-acetyl-LTE4 in four different HPLC solvent systems. The identity of endogenous N-acetyl-LTE4 elicited by endotoxin in vivo was additionally verified by enzymatic deacetylation followed by chemical N-acetylation. The deacetylation was catalyzed by penicillin amidase. Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation. A N-acetyl-LTE4 concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection. Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE4. The mercapturic acid pathway, leading from the glutathione conjugate LTC4 to N-acetyl-LTE4, thus plays an important role in the deactivation and elimination of these potent endogenous mediators.

• Research Organization: Universitaet Freiburg, West Germany
• OSTI ID: 5531846
• Journal Information: Prostaglandins; (United States), Journal Name: Prostaglandins; (United States) Vol. 2; ISSN PRGLB
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLATION
ACYLATION
AMIDASES
ANIMALS
ANTIGENS
ARACHIDONIC ACID
BILE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BODY FLUIDS
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DRUGS
ENDOTOXINS
ENZYMES
HYDROLASES
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MATERIALS
METABOLITES
MONOCARBOXYLIC ACIDS
NON-PEPTIDE C-N HYDROLASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RATS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTORS
VERTEBRATES