TY - JOUR
T1 - Metabolism of leukotriene B4 in the monkey. Identification of the principal nonvolatile metabolite in the urine
AU - Serafin, William E.
AU - Oates, John A.
AU - Hubbard, Walter C.
N1 - Funding Information:
We would like to thank Ms. Ella Stitt and Mr. William Herzer for their superb technical assistance and Mr. 3ohn Lawson for his participation in the gas chromatography-mass spectroscopic analysis. We acknowledge the helpful suggestions of Drs. L..~. Roberts, A.R. Brash, and E. K. 3ackson in the experimental design of these studies. This work was supported by National Institutes of Health grants AM-28511, GM-07569, and SO7-RR05424. 3.A.O. is the 3oe and Morris Werthan Professor of Investigative Medicine.
PY - 1984/6
Y1 - 1984/6
N2 - Five milligrams of [5,6,8,9,11,12,14,15-3H8]-leukotriene B4 (LTB4) (1.68 Ci/mmol) were infused into a monkey over a three hour period. Twenty-five per cent of the infused 3H-activity was recovered in the urine during the twenty hours of collection. Plasma and urinary metabolite volatility studies revealed that in contrast to previously studied eicosanoids, more than 70% per cent of the infused LTB4 3H-label was converted to tritiated water. The major nonvolatile urinary metabolite of LTB4 representing 0.8% of the infused material was identified as 20-OH-LTB4. LTB4 was not excreted in the urine. Other nonvolatile metabolites of LTB4 representing less than 0.4% each of the infused material were isolated from the urine. While there was an adequate quantity of some of these metabolites for partial characterization, there was insufficient material for structural elucidation. Further studies were performed in rabbits in which either LTB4 or the structurally related compound 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE) were infused intravenously. In these rabbits the metabolism of LTB4 and 8,15-diHETE was similar to that in the monkey with greater than 80% of the infused 3H-activity converted to tritiated water. These studies suggest that leukotriene B4 and structurally related compounds undergo extensive degradation in vivo via the β-oxidation system.
AB - Five milligrams of [5,6,8,9,11,12,14,15-3H8]-leukotriene B4 (LTB4) (1.68 Ci/mmol) were infused into a monkey over a three hour period. Twenty-five per cent of the infused 3H-activity was recovered in the urine during the twenty hours of collection. Plasma and urinary metabolite volatility studies revealed that in contrast to previously studied eicosanoids, more than 70% per cent of the infused LTB4 3H-label was converted to tritiated water. The major nonvolatile urinary metabolite of LTB4 representing 0.8% of the infused material was identified as 20-OH-LTB4. LTB4 was not excreted in the urine. Other nonvolatile metabolites of LTB4 representing less than 0.4% each of the infused material were isolated from the urine. While there was an adequate quantity of some of these metabolites for partial characterization, there was insufficient material for structural elucidation. Further studies were performed in rabbits in which either LTB4 or the structurally related compound 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE) were infused intravenously. In these rabbits the metabolism of LTB4 and 8,15-diHETE was similar to that in the monkey with greater than 80% of the infused 3H-activity converted to tritiated water. These studies suggest that leukotriene B4 and structurally related compounds undergo extensive degradation in vivo via the β-oxidation system.
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U2 - 10.1016/S0090-6980(84)80009-X
DO - 10.1016/S0090-6980(84)80009-X
M3 - Article
C2 - 6091183
AN - SCOPUS:0021284662
SN - 0090-6980
VL - 27
SP - 899
EP - 911
JO - Prostaglandins
JF - Prostaglandins
IS - 6
ER -