Endogenous morphine and ACTH association in neural tissues

Background: Endogenous morphine and proopiomelanocortin-derived peptide-like molecules were identified in molluscan tissues, including the nervous system, supporting their ancient phylogeny. Their presence and function in simple animals, demonstrates their involvement in mechanisms underlying the stress response, preceding the mammalian neuroendocrine axis. Methods: Immunocytochemical analysis was used to study the localization of morphine- and adrenocorticotropic hormone (ACTH)-like material in the nervous system of Planorbarius corneus, Mytilus galloprovincialis, Lymnaea stagnalis and Viviparus ater. Acute stress experiments were performed oil P. corneus and, by radioimmune assay, we quantified the expression of all ACTH-like peptide in control and stressed animals. Results: We demonstrate that in mollusks the presence of a morphine-like compound is differentially distributed in neuronal structures containing all ACTH-like molecule. In P corneus, the two immunoreactivities appear to be colocalized in neuronal bodies and axonal endings, suggesting a role in neurotransmission/neuromodulation. We also found that these molecules are released in the hemolymph, suggesting neuroendocrine-immunoregulatory communication. Comparative studies on the other mollusks gave different distribution pictures of the two immunoreactivities. In R corneus, following experimental trauma, the levels of both the messengers increase in ganglia and hemolymph at different times, which can be related to their postulated roles. Conclusion: In mollusks more than in mammals, there is a diversified but close association between morphine and ACTH, both acting in a stress response possibly exerting reciprocal influences, suggesting that the relationship evolved in invertebrates and was conserved during evolution.