21 Neuroendocrinology Letters ISSN 0172–780X Copyright © 2002 Neuroendocrinology Letters INVITED NEL REVIEW invited nel review A Hormonal Role for Endogenous Opiate Alkaloids: Vascular Tissues George B. Stefano, 1,2 Wei Zhu, 1 Patrick Cadet, 1 Kirk Mantione, 1 Thomas V. Bilfinger, 1,2 Enrica Bianchi 3 & Massimo Guarna 3 1.Neuroscience Research Institute, State University of New York/ College at Old Westbury, Old Westbury, New York, 11568 USA. 2. Cardiothoracic Division, Department of Surgery, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York, 11794. USA. 3. Department of Biomedical Sciences and Institute of Neurological and Psychiatric Diseases, University of Siena, Italy. Correspondence to: Prof. George B. Stefano, Ph. D. Neuroscience Research Institute, State University of New York, College at Old Westbury, Old Westbury NY 11568, USA. TEL +1 516-876-2732; FAX +1 516-876-2727; E-MAIL gstefano@sunynri.org Submitted: February 4, 2002 Accepted: February 4, 2002 Key words: morphine; vascular endothelial cells; adrenal gland; nitric oxide Neuroendocrinology Letters 2002; 23:21–26 pii: NEL230102R02 Copyright © Neuroendocrinology Letters 2002 Abstract The distribution of morphine-containing cells in the central nervous system, adrenal gland, and its presence in blood may serve to demonstrate that this signal molecule can act as a hormone besides its role in cell-to-cell signaling within the brain. This speculative review is the result of a literature evalu- ation with an emphasis on studies from our laboratory. Opioid peptides and opiate alkaloids have been found to influence cardiac and vascular func- tion. They have also been reported to promote ischemic preconditioning protection in the heart. Given the presence of morphine and the novel μ 3 opiate receptor on vascular endothelial cells, including cardiac and vascular endothelial cells in the median eminence, it would appear that endogenous opiate alkaloids are involved in modulating cardiac function, possible at the hormonal level. This peripheral target tissue, via nitric oxide coupling to μ opiate receptors, may serve to down regulate the excitability of this tissue given the heart’s high performance state as compared to that of the saphe- nous vein, a passive resistance conduit. With this in mind, morphine and other endogenous opiate alkaloids may function as a hormone.