Histamine stimulation of prostaglandin and HETE synthesis in human endothelial cells.
Endothelial cells (EC) cultured from human umbilical artery (UA) and vein (UV) metabolized [14C]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 [14C]PGs and [14C]HETEs from [14C]arachidonic acid-labeled ECs. Indomethacin, aspirin, and nordihydroguauretic acid completely inhibited synthesis of both [14C]PGs and [14C]HETEs from exogenous [14C]arachidonic acid in these cells. Microsomes metabolized [14C]arachidonic acid to the same [14C]PGs and [14C]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.
Revtyak
G E
GE
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Hughes
M J
MJ
Johnson
A R
AR
Campbell
W B
WB
D001095:Arachidonic Acids / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D011738:Pyrilamine / Q000494:pharmacology; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D006632:Histamine; D011738:Pyrilamine