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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-05-1444. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1444v1 100/12/4040    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maccarrone, M. Articles by Finazzi-Agrò, A. Search for Related Content PubMed PubMed Citation Articles by Maccarrone, M. Articles by Finazzi-Agrò, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 4040-4048 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Estrogen stimulates arachidonoylethanolamide release from human endothelial cells and platelet activation Mauro Maccarrone, Monica Bari, Natalia Battista, and Alessandro Finazzi-Agrò From the Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy. 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 × mg protein1, 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. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A A Izzo and M Camilleri Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects Gut, August 1, 2008; 57(8): 1140 - 1155. [Abstract] [Full Text] [PDF] L. Adermark and D. M. Lovinger Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step PNAS, December 18, 2007; 104(51): 20564 - 20569. [Abstract] [Full Text] [PDF] A.H. Taylor, C. Ang, S.C. Bell, and J.C. Konje The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy Hum. Reprod. Update, September 1, 2007; 13(5): 501 - 513. [Abstract] [Full Text] [PDF] G. Rossi, V. Gasperi, R. 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