Endogenous codeine and morphine are stored in specific brain neurons

Bianchi, Enrica; Alessandrini, C.; Guarna, Massimo; Tagliamonte, A.

doi:10.1016/0006-8993(93)90323-f

Cited by 43 publications

(22 citation statements)

References 9 publications

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“…For alkaloidinjected mice, MIR density gradients in cells, extracellular space, and processes were dependent on the distance from the injection site (LV, lateral ventricle; data not shown). These results are consistent with those of previous studies showing that exogenous morphine can be stored in cells containing endogenous morphine (Bianchi et al, 1993).…”

Section: Endogenous Alkaloids Mapping In the Mouse Brainsupporting

confidence: 95%

“…Since this discovery, many publications have characterized the presence of endogenous morphine and codeine in mammals (Goldstein et al, 1985;Spector et al, 1985;Cardinale et al, 1987;Donnerer et al, 1987;Bianchi et al, 1993;Molina et al, 1995;Muller et al, 2008). In the present paper a mass spectrometry approach (red) with GFAP (green) in the cortex proving the presence of MIR in astrocytes and astrocytic feet around blood vessels (arrow).…”

Section: Discussionmentioning

confidence: 78%

“…This is supported by the previously published description of Ca 2þ -dependent release of morphine from nerve terminals (Guarna et al, 1998). Other studies have also shown the presence of morphine and codeine in specific brain neurons (Gintzler et al, 1978;Bianchi et al, 1993Bianchi et al, , 1994. This further suggests that endogenous morphine and its derivatives may represent new neuromodulators of brain functions, acting at both pre-and postsynaptic sites within neuronal networks.…”

Section: Introductionmentioning

confidence: 63%

“…These results are similar to those of previously published studies of the localization of endogenous alkaloids in the mouse brain. (Gintzler et al, 1978;Bianchi et al, 1993Bianchi et al, , 1994Stefano et al, 2000;Muller et al, 2008). By using classical confocal and electron microscopy, we were able to characterize different structures and cells containing endogenous morphine-like compounds.…”

Section: Discussionmentioning

confidence: 99%

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Mapping of endogenous morphine‐like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

Laux

Muller

Miehe

et al. 2011

J of Comparative Neurology

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Endogenous morphine, morphine-6-glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine and its derivative compounds is a matter of debate, and knowledge about its distribution is lacking. In this study, by using a validated antibody, we describe a precise mapping of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the mouse brain. First, a mass spectrometry approach confirmed the presence of morphine and codeine in mouse brain, but also, of morphine-6-glucuronide and morphine-3-glucuronide representing two metabolites of morphine. Second, light microscopy allowed us to observe immunopositive cell somas and cytoplasmic processes throughout the mouse brain. Morphine-like immunoreactivity was present in various structures including the hippocampus, olfactory bulb, band of Broca, basal ganglia, and cerebellum. Third, by using confocal microscopy and immunofluroscence co-localization, we characterized cell types containing endogenous opiates. Interestingly, we observed that morphine-like immunoreactivity throughout the encephalon is mainly present in γ-aminobutyric acid (GABA)ergic neurons. Astrocytes were also labeled throughout the entire brain, in the cell body, in the cytoplasmic processes, and in astrocytic feet surrounding blood vessels. Finally, ultrastructural localization of morphine-like immunoreactivity was determined by electron microscopy and showed the presence of morphine-like label in presynaptic terminals in the cerebellum and postsynaptic terminals in the rest of the mouse brain. In conclusion, the presence of endogenous morphine-like compounds in brain regions not usually involved in pain modulation opens the exciting opportunity to extend the role and function of endogenous alkaloids far beyond their analgesic functions.

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Section: Endogenous Alkaloids Mapping In the Mouse Brainsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Mapping of endogenous morphine‐like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

Laux

Muller

Miehe

et al. 2011

J of Comparative Neurology

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“…In vertebrates, catechol O-methyl transferase (COMT) from the morphine pathway is modified to accommodate norepinephrine (NE) to form epinephrine (E). Furthermore, highlighting this relationship even further is an association of catecholamine brain localization with that of endogenous morphine (16,18,29,(59)(60)(61)(62)(63)(64)(65). This association may be predicted from the fact that DA is an endogenous morphine precursor, and the ability of morphine-induced NO to downregulate excitatory processes and scavenge free radicals, in part, is associated with catecholamine signaling (28,42).…”

Section: Enzyme Evolvementmentioning

confidence: 99%

Endogenous morphine synthetic pathway preceded and gave rise to catecholamine synthesis in evolution (Review)

Stefano¹,

Kream²

2007

Int J Mol Med

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Abstract. The biological presence and regulatory function of the plant alkaloid morphine in relatively simple and complex integrated animal systems has previously been shown. The pivotal role of dopamine as a chemical intermediate in the morphine biosynthetic pathway in plants establishes a functional basis for its expansion into an essential role as the progenitor catecholamine signaling molecule. In invertebrate neural systems, dopamine serves as the preeminent catecholamine signaling molecule, with the emergence and limited utilization of norepinephrine and its biosynthetic enzyme dopamine ß-hydroxylase in newly defined adaptational chemical circuits required by a rapidly expanding set of physiological demands. In vertebrates, epinephrine emerges as the major end of the catecholamine synthetic pathway consistent with a newly incorporated regulatory modification, i.e. N-methylation of norepinephrine. Given the striking similarities between the enzymatic steps in the morphine biosynthetic pathway and those driving the evolutionary adaptation of catecholamine chemical species to accommodate an expansion of interactive but distinct signaling systems, we surmise that the evolutionary emergence of catecholamine systems required conservation and selective 'retrofit' of specific enzyme activities, i.e. catechol O-methyl transferase and phenylethanol-amine N-methyl transferase, drawn from cellular morphine expression. This hypothesis is further supported by the critical recruitment of enzymatically synthesized tetrahydrobiopterin (BH4) both as an essential cofactor for tyrosine hydroxylase-mediated dopamine production and as a secondary electron donor for nitric oxide synthase-mediated nitric oxide (NO) production. The establishment of a reciprocal regulatory linkage between NO and catecholaminergic processes, as mediated by BH4, subserves a pivotal capacity to promote autocrine and paracrine regulation of signaling molecules. In summary, ongoing development and adaptation of catecholamine signaling pathways in animals appear to be related to their mobile lifestyle associated with complex feeding, sexual and protective processes, which also generate free radicals, thus requiring morphinergic signaling coupling to NO release.

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Localization of endogenous morphine‐like compounds in the mouse spinal cord

Laux¹,

Delalande²,

Mouheiche³

et al. 2012

J of Comparative Neurology

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Morphine, codeine, morphine-6-glucuronide, and morphine-3-glucuronide are synthesized de novo in mammalian cells and in the central nervous system. Knowledge on endogenous morphine-like compound distribution in the adult mouse brain has been recently improved, and new hypotheses have been suggested about the potential implications in brain physiology. Endogenous morphine-like compounds have been shown to be synthesized in the spinal cord, but their localization is unknown. Here we describe the distribution of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the adult mouse spinal cord using a well-validated antibody. By using different microscopy approaches, we found the presence of morphine, codeine, or morphine glucuronides in γ-aminobutyric acid (GABA)-ergic neurons and astrocytes of the spinal cord. Whereas GABAergic neurons containing endogenous morphine-like compounds were located primarily in the ventral horn, astrocytes that were labeled for morphine-like compounds were found throughout the gray matter and the white matter. Our study demonstrates the possibility that endogenous morphine-like compounds in the central nervous system have other functions beyond their analgesic functions.

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Endogenous codeine and morphine are stored in specific brain neurons

Cited by 43 publications

References 9 publications

Mapping of endogenous morphine‐like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

Mapping of endogenous morphine‐like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

Endogenous morphine synthetic pathway preceded and gave rise to catecholamine synthesis in evolution (Review)

Localization of endogenous morphine‐like compounds in the mouse spinal cord

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