Regulation of synthesis of prostacyclin and HETEs in human endothelial cells. Am J Physiol 1989 Jun;256(6 Pt 1):C1168-75
Date
06/01/1989Pubmed ID
2500022DOI
10.1152/ajpcell.1989.256.6.C1168Scopus ID
2-s2.0-0024402914 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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. Indomethacin 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 microM for PGI2, 0.25 microM for 15-HETE, and 0.10 microM 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.
Author List
Ibe BO, Falck JR, Johnson AR, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
6-Ketoprostaglandin F1 alphaArachidonic Acid
Arachidonic Acids
Bradykinin
Calcimycin
Cells, Cultured
Cross Reactions
Endothelium, Vascular
Epoprostenol
Histamine
Humans
Hydroxyeicosatetraenoic Acids
Immune Sera
Kinetics
Melitten
Prostaglandin Antagonists