Regulation of synthesis of prostacyclin and HETEs in human endothelial cells

B. O. Ibe, J. R. Falck, A. R. Johnson, W. B. Campbell

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Human umbilical endothelial cells in culture synthesize prostacyclin (PGI2), 15-hydroxyeicosatetraenoic acid (15-HETE), and 12-hydroxyeicosatetraenoic acid (12-HETE). The synthesis of these eicosanoids was measured by specific radioimmunoassays after stimulation by arachidonic acid, A23187, bradykinin, melittin, or histamine. Under all conditions, the synthesis of PGI2 paralleled and exceeded the synthesis of 15-HETE and 12-HETE. Idomethacin inhibited arachidonic acid-stimulated PGI2 and 15-HETE synthesis but enhanced 12-HETE synthesis. Meclofenamate gave similar qualitative results. Drugs that act as inhibitors of lipoxygenase in some tissues, such as nordihydroguaiaretic acid (NDGA), caffeic acid, esculin-diethylcarbamazine, quercetin, and 5,8,11,14-eicosatetrayenoic acid (ETYA) were nonspecific in their inhibition of PGI2, 12-HETE, and 15-HETE synthesis. For example, NDGA inhibited arachidonic acid-stimulated release with a 50% inhibitory concentration (IC50) of 0.39 μM for PGI2, 0.25 μM for 15-HETE, and 0.10 μM for 12-HETE. These results show that endothelial cells metabolize both endogenous and exogenous arachidonic acid to PGI2, 15-HETE, and 12-HETE. These data also suggest, based on results with inhibitors, that PGI2 and 15-HETE are products of cyclooxygenase, whereas 12-HETE is produced via a different enzymatic pathway, most likely a lipoxygenase pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume256
Issue number6
StatePublished - 1989

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Hydroxyeicosatetraenoic Acids
Endothelial cells
Epoprostenol
Endothelial Cells
Arachidonic Acid
Masoprocol
Inhibitory Concentration 50
Esculin
Meclofenamic Acid
Diethylcarbamazine
Melitten
Umbilicus
Lipoxygenase Inhibitors
Lipoxygenase
Eicosanoids
Quercetin
Calcimycin
Bradykinin
Prostaglandin-Endoperoxide Synthases
Cell culture

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Regulation of synthesis of prostacyclin and HETEs in human endothelial cells. / Ibe, B. O.; Falck, J. R.; Johnson, A. R.; Campbell, W. B.

In: American Journal of Physiology - Cell Physiology, Vol. 256, No. 6, 1989.

Research output: Contribution to journalArticle

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