Histamine stimulation of prostaglandin and HETE synthesis in human endothelial cells
Endothelial cells (EC) cultured from human umbilical artery (UA) and vein (UV) metabolized (/sup 14/C)arachidonic acid to prostaglandins (PGs), monohydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Major radioactive products were identified as 6-keto-PGF1 alpha, PGE2, PGF2 alpha, 12-hydroxy heptadecatrienoic acid, 15-HETE, and 11-HETE. In addition, extracts from UV ECs contained 12-HETE, 5-HETE, 14,15-EET, and 5,6-EET as minor products, whereas extracts from UA ECs contained only 12-HETE as a minor product. UA ECs also produced metabolites comigrating with 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. Histamine increased the release of (/sup 14/C)PGs and (/sup 14/C)HETEs from (/sup 14/C)arachidonic acid-labeled ECs. Indomethacin, aspirin, and nordihydroguauretic acid completely inhibited synthesis of both (/sup 14/C)PGs and (/sup 14/C)HETEs from exogenous (/sup 14/C)arachidonic acid in these cells. Microsomes metabolized (/sup 14/C)arachidonic acid to the same (/sup 14/C)PGs and (/sup 14/C)HETEs as intact cells. Pretreatment of microsomes with indomethacin completely inhibited formation of these products. These data indicate that UA ECs and UV ECs metabolize endogenous and exogenous arachidonic acid to both PGs and HETEs. Also 15-HETE and 11-HETE appear to be synthesized by a microsomal enzyme with the properties of cyclooxygenase.
- Research Organization:
- Univ. of Texas Southwestern Medical Center, Dallas (USA)
- OSTI ID:
- 6864669
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 255; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL TISSUES
ARACHIDONIC ACID
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
EICOSANOIC ACID
ENDOTHELIUM
HETEROCYCLIC COMPOUNDS
HISTAMINE
IMIDAZOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
METABOLISM
MICROSOMES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
PREGNANCY
PROSTAGLANDINS
REACTION KINETICS
SYNTHESIS
TISSUES
TRACER TECHNIQUES