11,12-Epoxyeicosatrienoic acid activates the L-arginine/nitric oxide pathway in human platelets.
The present study was to test the hypothesis that 11,12-epoxyeicosatrienoic acid (11,12-EET), a metabolic product of arachidonic acid by cytochrome P450 epoxygenase, regulates nitric oxide (NO) generation of the L-arginine/NO synthase (NOS) pathway in human platelets. Human platelets were incubated in the presence or absence of different concentrations of 11,12-EET for 2 h at 37 degrees C, followed by measurements of activities of the L-arginine/NOS pathway. Incubation with 11,12-EET increased the platelet NOS activity, nitrite production, cGMP content, and the platelet uptake of L-[(3)H]arginine in a concentration-dependent manner. In addition, 11,12-EET attenuated intracellular free Ca(2+) accumulation stimulated by collagen, which was at least partly mediated by EET-activated L-arginine/NOS pathway. It is suggested that 11,12-EET regulates platelet function through up-regulating the activity of the L-arginine/NOS/NO pathway.
Zhang
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Department of Pathophysiology, Capital University of Medical Sciences, Beijing 100069, People's Republic of China. zlk30@tom.com
Cui
Yuying
Y
Geng
Bing
B
Zeng
Xiangjun
X
Tang
Chaoshu
C
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D014316:Tritium
D009566:Nitrates; D009573:Nitrites; D014316:Tritium; D009569:Nitric Oxide; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003094:Collagen; D001120:Arginine; D019001:Nitric Oxide Synthase; D015126:8,11,14-Eicosatrienoic Acid; D006152:Cyclic GMP