Evidence of opiates and opioid neuropeptides and their immune effects in parasitic invertebrates representing three different phyla: Schistosoma mansoni, Theromyzon tessulatum, Trichinella spiralis.

Studies done in our laboratories have demonstrated that the parasitic trematode, Schistosoma mansoni is capable of producing several proopiomelanocortin (POMC) peptides including beta-endorphin, adrenocorticotropin (ACTH), melanocyte stimulating hormone (alphaMSH) and enkephalin as well as morphine. Some of these opioids have been demonstrated to be immunosuppressive and may play an important part in immune evasion by these parasites. The parasitic nematode Trichinella spiralis also produces immune suppressive substances in vitro as well as causes immune suppression in its encysted stage in vivo. We recently have demonstrated the presence of morphine in both infected mice and in the nematode by HPLC and RIA. In a recent study of the leech Theromyzon tessulatum, we demonstrated the presence of proopiomelanocortin (POMC) and its derived peptides, ACTH and alphaMSH, in the immune tissues. The peptide was cloned and extensively purified by HPGPC and reversed-phase HPLC, and then sequenced. The 25.4 kDa protein was purified by gel permeation chromatography, anti-ACTH-affinity column separation followed by reversed-phase HPLC. Its amino acid determination was performed by Edman degradation, enzymatic treatments and electrospray mass spectrometry. The structure of the leech POMC-like precursor and its derived peptides demonstrates considerable amino acid sequence similarity with mammalian POMC. Taken together, these studies demonstrate that opiates and opioid neuropetides are present in invertebrates and their immunoregulatory actions have been conserved during evolution. The role of opiates and opioid peptides in immune and behavior modification of hosts is also discussed.