Review paper Opioid peptides and opiate alkaloids in immunoregulatory processes George B. Stefano, Richard M. Kream Neuroscience Research Institute, State University of New York, College at Old Westbury, Old Westbury, USA Submitted: 13 May 2010 Accepted: 11 June 2010 Arch Med Sci 2010; 6, 3: 456-460 DOI: 10.5114/aoms.2010.14271 Copyright © 2010 Termedia & Banach A b s t r a c t Among the various non-neuronal cell types known to express and utilize neuropeptides, those of the immune system have received much attention in recent years. In particular, comparative studies in vertebrates and invertebrates have shown that endogenous opioid peptides are engaged in receptor mediated autoregulatory immune and neuroendocrine processes. The majority of these immune processes are stimulatory, as determined by their effects on conformational changes indicative of immunocyte activation, cellular motility, and phagocytosis. Endogenous opioid peptides form an effective network of messenger molecules in cooperation with cytokines, opiate alkaloids, and certain regulatory enzymes (neutral endopeptidase 24.11). Peptide-mediated immunostimulatory effects observed in this system are operationally counteracted by the inhibitory effects of morphine and related opiates. Opioid/opiate signaling processes are mediated by several types of receptors with different degrees of selectivity. Among them the recently identified, opioid insensitive µ 3 receptor deserves attention on account of its specificity for opiate alkaloids. Key words: opioid peptides, morphine, leukocytes, immunoregulation, invertebrate immune cells, G protein, neutral endopeptidase. Introduction There is a growing realization in biological sciences that neuropeptides, formerly thought to be produced by a select group of neurons, are found in a variety of non-neuronal cells. Comparative studies in vertebrates and invertebrates [1-4] have highlighted the biological importance of immunoactive cells which make use of neuropeptides for autoregulatory control as well as the bidirection exchange of information between the immune system and the neuroendocrine system. Along with cytokines, long considered to be the primary messenger molecules of the immune system, endogenous opioid peptides form an effective network of communication. Previous studies demonstrated the presence of opioid peptides and opiate alkaloids in both invertebrate and vertebrate nervous and immune systems along with highly selective types of opioid receptors [5-9]. Functional aspects Biological activities associated with proinflammatory processes that have been analyzed in detail in higher invertebrates as well as vertebrates Corresponding author: George B. Stefano Neuroscience Research Institute State University of New York Old Westbury NY 11568, USA Phone: 516-876-2732 Fax: 516-876-2727 E-mail: gstefano@sunynri.org