Estrogen stimulates arachidonoylethanolamide release from human endothelial cells and platelet activation

Mauro Maccarrone, Monica Bari, Natalia Battista, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, though the mechanism for this benefit remains unclear. Here we show that at physiological concentrations estrogen activates the anandamide membrane transporter of human endothelial cells and leads to rapid elevation of calcium (apparent within 5 minutes) and release of nitric oxide (within 15 minutes). These effects are mediated by estrogen binding to a surface receptor, which shows an apparent dissociation constant (Kd) of 9.4 ± 1.4 nM, a maximum binding (Bmax) of 356 ± 12 fmol x mg protein-1, and an apparent molecular mass of approximately 60 kDa. We also show that estrogen binding to surface receptors leads to stimulation of the anandamide-synthesizing enzyme phospholipase D and to inhibition of the anandamide-hydrolyzing enzyme fatty acid amide hydrolase, the latter effect mediated by 15-lipoxygenase activity. Because the endothelial transporter is shown to move anandamide across the cell membranes bidirectionally, taken together these data suggest that the physiological activity of estrogen is to stimulate the release, rather than the uptake, of anandamide from endothelial cells. Moreover, we show that anandamide released from estrogen-stimulated endothelial cells, unlike estrogen itself, inhibits the secretion of serotonin from adenosine diphosphate (ADP)-stimulated platelets. Therefore, it is suggested that the peripheral actions of anandamide could be part of the molecular events responsible for the beneficial effects of estrogen.

Original languageEnglish
Pages (from-to)4040-4048
Number of pages9
JournalBlood
Volume100
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

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Endothelial cells
Platelet Activation
Platelets
Estrogens
Endothelial Cells
Chemical activation
Arachidonate 15-Lipoxygenase
Phospholipase D
Estrogen Replacement Therapy
Membrane Transport Proteins
Enzymes
anandamide
Molecular mass
Adenosine Diphosphate
Cell membranes
Serotonin
Nitric Oxide
Blood Platelets
Cell Membrane
Calcium

ASJC Scopus subject areas

  • Hematology

Cite this

Estrogen stimulates arachidonoylethanolamide release from human endothelial cells and platelet activation. / Maccarrone, Mauro; Bari, Monica; Battista, Natalia; Finazzi-Agrò, Alessandro.

In: Blood, Vol. 100, No. 12, 01.12.2002, p. 4040-4048.

Research output: Contribution to journalArticle

Maccarrone, Mauro ; Bari, Monica ; Battista, Natalia ; Finazzi-Agrò, Alessandro. / Estrogen stimulates arachidonoylethanolamide release from human endothelial cells and platelet activation. In: Blood. 2002 ; Vol. 100, No. 12. pp. 4040-4048.
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