Multiple opioid receptors on immune cells modulate intracellular signaling

In 1979, Joseph Wybran reported his insights into the existence of different opioid receptor subtypes on T-cells. He observed that morphine and methionine enkephalin had different effects on human T-cell rosetting to sheep red blood cells. Since that time, a wide array of laboratories have shown that opiate alkyloids and opioid peptides exert pleiotropic effects on immune cell function. These compounds are immunomodulators, modifying immune responses to extracellular stimuli such as mitogens, antigens, and antibodies that cross-link the T-cell receptor. It has been demonstrated that cells involved in host defense and immunity express mRNA transcripts encoding the various opioid receptors originally described in neuronal tissues. Molecular imaging approaches have demonstrated the regulated expression of both delta and kappa opioid receptors, predominantly on T-cells. Moreover, atypical opiate and opioid binding sites are present on these cells. This review will consider the evidence for both classical and atypical opioid receptors and their effects on signaling within immune cells; our emphasis is the T-cell and its delta opioid receptor.