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Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells. Biochim Biophys Acta 1985 Oct 23;837(1):67-76 PMID: 3931686

Pubmed ID

3931686

Abstract

Human umbilical vein endothelial cells were found to contain adrenic acid (22:4) in their cellular lipids. Since this fatty acid may be metabolized by cyclooxygenase in the kidney, the metabolism of adrenic acid was studied in endothelial cell cultures. [14C]Adrenic acid was metabolized to several more polar metabolites. Two of these metabolites co-migrated on HPLC with 1 alpha,1 beta-dihomo-8-ketoprostaglandin F1 alpha (the metabolite of 1 alpha, 1 beta-dihomoprostaglandin I2) and 1 alpha,1 beta-dihomoprostaglandin E2. Indomethacin (10(-5) M) inhibited the synthesis of these metabolites. When cells were treated with adrenic acid (3 X 10(-5) M), a peak that co-migrated with dihomo-8-ketoprostaglandin F1 alpha was detected by radioimmunoassay using an antiserum directed against 6-ketoprostaglandin F1 alpha. The presence of dihomo-8-ketoprostaglandin F1 alpha was confirmed by gas chromatography-mass spectrometry. Immunoreactive peaks that co-migrated with dihomoprostaglandins E2 and F2 alpha were identified with antisera against prostaglandin E2 and prostaglandin F2 alpha, respectively. [14C]Arachidonic acid was metabolized to [14C]prostaglandin F2 alpha, 6-keto[14C]prostaglandin F1 alpha, and [14C]prostaglandin E2. Similar results were found with unlabelled arachidonic acid using specific antisera. When the two fatty acids were combined, adrenic acid reduced the metabolism of arachidonic acid. The culture media from endothelial cells inhibited thrombin-induced platelet aggregation, an effect blocked by aspirin. The inhibitory activity of the media was enhanced when arachidonic acid was added to the cells, but it was reduced by adrenic acid. Both prostaglandin I2 and dihomoprostaglandin I2 inhibited platelet aggregation, but prostaglandin I2 was 100-times more potent. We conclude that adrenic acid is metabolized in human endothelial cells to 1 alpha, 1 beta-dihomoprostaglandins and can compete with endogenous arachidonic acid for conversion by cyclooxygenase. These findings suggest that adrenic acid may reduce the formation of prostaglandin I2 by the blood vessel.

Author List

Campbell WB, Falck JR, Okita JR, Johnson AR, Callahan KS

Author

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-0021947113   41 Citations

MESH terms used to index this publication - Major topics in bold

Arachidonic Acid
Arachidonic Acids
Cells, Cultured
Culture Media
Dinoprostone
Endothelium
Epoprostenol
Erucic Acids
Fatty Acids
Fatty Acids, Unsaturated
Humans
Indomethacin
Platelet Aggregation
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Prostaglandins E
Prostaglandins F, Synthetic
Thrombin
Umbilical Veins
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e