Search

Cultures of isolated neuronal populations from the central ganglia of the gastropod mollusc Planorbarius corneus were used for testing the effects of inorganic lead. The examined parameters were cell survival, neurite outgrowth and cytoskeletal morphology. In large heterogeneous neuronal populations as obtained from a whole cerebral or pedal ganglion, the different sensitivity to lead is reflected mainly on the cell survival. The neurons belonging to the homogeneous E cluster population are more sensitive; in fact a higher percentage of them do not survive in the presence of lead. Moreover, in this neuronal cell type the neurite outgrowth is dramatically affected by lead only when the neurons are cultured on conditioned substrate. Possibly, membrane mechanisms activated for the neurite outgrowth represent a target for inorganic lead. The few neurites sprouted in presence of lead do not evidence changes in the cytoskeletal components.

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.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 on P. corneus and, by radioimmune assay, we quantified the expression of an ACTH-like peptide in control and stressed animals.We demonstrate that in mollusks the presence of a morphine-like compound is differentially distributed in neuronal structures containing an 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 P. 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.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.

Morphine is the most used compound among narcotic analgesics. Apart from its presence in the poppy plant, morphine has been shown to be endogenously present in different tissues of mammals and lower animals.The presence of endogenous morphine and codeine was investigated by Gas Chromatography/ Mass Spectrometry (GC/MS) in the brain of non human primate. The release of endogenous morphine from monkey brain slices was studied in vitro in the presence of high potassium concentrations with and without calcium in the medium.Endogenous morphine, and its direct precursor codeine, was for the first time detected by GC/MS in the brain of non human primate. High potassium concentrations depolarized neurons releasing endogenous morphine twofold above basal line levels in a calcium dependent mechanism.This finding confirms the presence of the endogenous alkaloid throughout the phylogenesis of the nerve system of mammals and lower animals and indicates that endogenous morphine might function as a neuromodulator/neurotransmitter agent in the central nervous system (CNS) of non human primates.

International audience; Background: The ability of animals to make morphine has been in question for the last 30 years. Studies have demonstrated that animals do contain morphine precursors and metabolites, as well as the ability to use some morphine precursors to make morphine.Material/methods: The present study uses excised ganglia from the marine invertebrate Mytilus edulis as well as whole animals. Morphine and dopamine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay. Tissues and whole animals were also exposed to morphine precursors and exposed to the CYP2D6 inhibitor quinidine and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Additionally, via RT-PCR, a cDNA fragment of the CYP2D6 enzyme in the ganglia of M. edulis was identified.Results: Pedal ganglia incubated with either tyramine or tyrosine, or whole animals receiving injections, exhibited a statistically significant concentration- and time-dependent increase in their endogenous morphine and dopamine levels (2.51 +/- 0.76 ng/g for tyrosine and 2.39 +/- 0.64 ng/g for tyramine compared to approximately 1.0 ng/g morphine wet weight). Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process. We also demonstrated that CYP2D6 mediates the tyramine to dopamine step in this process, as did tyrosine hydroxylase in the step from tyrosine to L-DOPA. Furthermore, via RT-PCR, we identified a cDNA fragment of the CYP2D6 enzyme in the ganglia, which exhibits 94% sequence identity with its human counterpart. Evidence that tyrosine and tyramine were, in part, being converted to dopamine then morphine, and that this process can be inhibited by altering either or both CYP2D6 or tyrosine hydroxylase, is also provided.Conclusions: It appears that animals have the ability to make morphine. This process also appears to be dynamic in that the inhibition of one pathway allows the other to continue with morphine synthesis. Moreover, dopamine and morphine synthesis were coupled.