Am. J. Biomed. Sci. 2009, 1(1), 27-37; doi: 10.5099/aj090100027 © 2009 by NWPII. All rights reserved. 27 American Journal of Biomedical Sciences ISSN: 1937-9080 nwpii.com/ajbms Estrogen and Morphine Modulate Their Own and the Other’s Human Endothelial Receptor Expression via Nitric Oxide Patrick Cadet 1 , Vincent Prevot 2 , Jean Claude Beauvillain 2 , Thomas V. Bilfinger 3 and George B. Stefano 1 1 Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, NY 11568, USA 2 INSERM, U422, IFR 22, Unité de Neuroendocrinologie et Physiopathologie Neuronale, Place de Verdun, 59045 Lille Cedex, France 3 Division of Cardiothoracic Surgery, Department of Surgery, State University of New York at Stony Brook, Stony Brook, NY *Corresponding Author: Dr. Patrick Cadet Neuroscience Research Institute, State University of New York - College at Old Westbury Old Westbury, NY 11568, USA Tel: 516-876-2739; Fax: 516-876-2727 Email: patcad@sunynri.org , Web: www.SUNYNRI.org Received: 6 November 2008; | Revised: 20 November 2008; | Accepted: 22 November 2008 Abstract In previous studies we have demonstrated that  3 and estrogen  receptor subtypes are present in human vascular endothelial cells and coupled to constitutive nitric oxide synthase (cNOS) stimulation. In the present report we demonstrate that internal thoracic artery (ITA) endothelia express a  opioid receptor mRNA transcript and exposure of these transcripts to increasing concentrations of 17 -estradiol significantly diminishes ITA  opioid receptor expression. Exposure of ITA endothelia to SNAP, a NO donor, also diminishes  opioid receptor gene expression, suggesting that NO mediates, in an L-NAME (N G - nitro-L-arginine methyl ester) and tamoxifen sensitive manner, 17 -estradiol‟s down regulating action. ITA endothelia also express an estrogen  receptor subtype and, when treated with morphine, in an L-NAME and naloxone sensitive manner diminishes the  estrogen receptor‟s expression. This demonstrates an interactive receptor mediated process via NO for both signaling agents. Additionally, morphine and estrogen actions were examined for their ability to alter adhesion to ITA segments. This treatment resulted in a concentration dependent decrease in monocyte adherence to the vessels at 30 min. Exposure to both agents did not decrease monocyte adherence further. Exposure to L-NAME or either naloxone or tamoxifen, opiate and estrogen cell surface receptor inhibitors, respectively, blocked the decrease in monocyte adherence, demonstrating NO involvement and a specific receptor mediated process. In conclusion, this study demonstrates that an interactive receptor mediated process via NO for both signaling agents is present. Keywords: 17--estradiol; tamoxifen; morphine; estrogen receptor; mu opiate receptor