Opiate-Like Substances in an Invertebrate, an Opiate Receptor on Invertebrate and Human Immunocytes, and a Role in Immunosuppression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 23; pp. 11099 - 11103
• Main Authors: Stefano, George B., Digenis, Alex, Spector, Sydney, Leung, Michael K., Bilfinger, Thomas V., Makman, Maynard H., Scharrer, Berta, Abumrad, Naji N.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-12-1993; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Binding, Competitive; Biochemistry. Physiology. Immunology; Biological and medical sciences; Bivalvia - physiology; Chemotaxis, Leukocyte - drug effects; Drugs; Fundamental and applied biological sciences. Psychology; Ganglia; Ganglia, Invertebrate - chemistry; Hemolymph; Hemolymph - chemistry; Humans; Immunity (Disease); Immunocytes; In Vitro Techniques; Invertebrates; Ligands; Marine; Mollusca; Mollusks; Monocytes; Monocytes - physiology; Morphine; Morphine - pharmacology; Mytilus edulis; Narcotics - pharmacology; Opiates; Opioid receptors; Physiology. Development; Receptors; Receptors, Opioid - physiology; Stress, Physiological - physiopathology; Human; Monocyte; Mytilus edulis; Homology; Morphine; Opioid peptide; Opiate receptor μ; Biological activity; Bivalvia; Immunocyte; Immunosuppressive agent; Invertebrata; Mollusca; Neuroimmunomodulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.23.11099

The presence of morphine-like and codeine-like substances was demonstrated in the pedal ganglia, hemolymph, and mantle tissues of the mollusc Mytilus edulis. The pharmacological activities of the endogenous morphine-like material resemble those of authentic morphine. Both substances were found to counteract, in a dose-dependent manner, the stimulatory effect of tumor necrosis factor α or interleukin 1α on human monocytes and Mytilus immunocytes, when added simultaneously to the incubation medium. The immunosuppressive effect of this opiate material expresses itself in a lowering of chemotactic activity, cellular velocity, and adherence. Codeine mimics the activity of authentic morphine, but only at much higher concentrations. Specific high-affinity receptor sites (μ3) for morphine have been identified on human monocytes and Mytilus immunocytes. In Mytilus recovering from experimentally induced stress, the return of "alerted" immunocytes to a more inactive state appears to be due to a significant rise in the content of morphine-like material in the pedal ganglia and hemolymph at this time. Thus, morphine may have a role in calming or terminating the state of immune alertness.