Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells

William B. Campbell, J R Falck, Janice R. Okita, Alice R. Johnson, Karleen S. Callahan

Research output: Contribution to journalArticle

43 Scopus citations

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 1α,1β-dihomo-8-ketoprostaglandin F (the metabolite of 1α,1β-dihomoprostaglandin I2) and 1α,1β-dihomoprostaglandin E2. Indomethacin (10-5M) inhibited the synthesis of these metabolites. When cells were treated with adrenic acid (3·10-5M), a peak that co-migrated with dihomo-8-ketoprostaglandin F was detected by radioimmunoassay using an antiserum directed against 6-ketoprostaglandin F. The presence of dihomo-8-ketoprostaglandin F1ga was confirmed by gas chromatography-mass spectrometry. Immunoreactive peaks that co-migrated with dihomoprostaglandins E2 and F were identified with antisera against prostaglandin E2 and prostaglandin F, respectively. [14C]Arachidonic acid was metabolized to [14C]prostaglandin F, 6-keto[14C]prostaglandin F, 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 1α,1β-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.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume837
Issue number1
DOIs
StatePublished - Oct 23 1985

Keywords

  • (Human endothelial cell)
  • Adrenic acid
  • Prostaglandin synthesis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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