<i>Ascaris suum</i>, an Intestinal Parasite, Produces Morphine

Goumon, Yannick; Casares, Federico; Pryor, Stephen C.; Ferguson, Lee M; Brownawell, Bruce J.; Cadet, Patrick; Rialas, Christos M.; Welters, Ingeborg; Sonetti, Dario; Stefano, George B.

doi:10.4049/jimmunol.165.1.339

Cited by 25 publications

(16 citation statements)

References 36 publications

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“…They emphasized that morphine production is a mechanism for immune evasion in these species they use HPLC the same as the others (Pryor and Elizee 2000). In the same year, Goumon et al did the similar investigation on Ascaris suum and detected the morphine-like substance by HPLC and gas chromatography/mass spectrometry (GC mass) method with the mean concentration of 1168±278 ng/ gwet weight, but they couldn't showed the existence of µ opioid receptor in this nematode (Goumon et al, 2000). There is another similar report two years later; the existence of opiate alkaloid morphine and also morphine 6-glucuronide (the active metabolite of morphine) in nematode D. medinensis and also trematode S. mansoni as a molecule for immunosuppressive of host but they used the other methods except HPLC for it, double quadrupole/orthogonal-acceleration, time-of-flight mass spectrometry and nano-electrospray-ionization (Zhu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for the presence of morphine like substance and μ opiate receptor expression in Dicrocoelium dendriticum (Trematoda: Dicrocoeliidae)

Mostafaei

Naem

Imani³

et al. 2018

J Hellenic Vet Med Soc

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Parasites for living in host’s body, evade from host’s immune system using variant methods such as production of some molecules with immunosuppressive properties. Of these immunosuppression molecules are morphine and morphine like substances. It can effect on innate and adaptive immunity and also humoral and cellular immunity. The past researches were approved the existence of morphine in the brain and adrenal of beef and in brain of mammalian and also it has been demonstrated as an immune modulator molecule in some invertebrates, some of the nematodes and also a trematode Schistosoma mansoni, But there is no document for morphine evidence in trematode Dicrocoelium dendriticum. Infection with this trematode has much importance either in health of ruminant and economic loos in the meat industry. In addition, this trematode is a zoonosis that there is no proper treatment for it in contrast with the other liver fluke, Fasciola hepatica. We assume that living for a long time in the bile ducts of host is related to morphine like substance as an immune regulatory molecule. We use RP-HPLC method for detection morphine in D. dendriticum and also using reverse transcription polymerase chain reaction (RT-PCR) for μ opioid receptor finding. According to the results D. dendriticum has endogenous morphine like material and also the existence of opioid μ receptor in this trematode was approved. Living in host bile duct for a long time without sever immunopathologycal impact, suggested that probably this worm use of morphine like material as an immunoregulatory molecule and also for escaping from host immune system.

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Section: Discussionmentioning

confidence: 99%

“…This solution were filtered by filter 0.2 micrometer for it clearance. Finally it was injected (Goumon et al, 2000).…”

Section: Sample Preparing For Hplcmentioning

confidence: 99%

Evidence for the presence of morphine like substance and μ opiate receptor expression in Dicrocoelium dendriticum (Trematoda: Dicrocoeliidae)

Mostafaei

Naem

Imani³

et al. 2018

J Hellenic Vet Med Soc

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“…morphine, M3G, and M6G, with minimal cross-reactivity to codeine as declared by the supplying company; 1:1000 dilution; Biogenesis, Bournemouth, UK) (8) in NaCl/P i buffer (0.9% (w/v) NaCl and 25 mM sodium phosphate, pH 7.5) containing 5% bovine serum albumin. Cells were then washed (6 ϫ 5 min) with NaCl/P i buffer and incubated with secondary antibodies (Cy5-conjugated donkey anti-rabbit IgG at 1:2000 dilution and Alexa 488-conjugated donkey anti-sheep IgG at 1:2000 dilution; Molecular Probes, Eugene, OR) in NaCl/P i buffer containing 5% bovine serum albumin for 45 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…In the 1990s, few groups succeeded in characterizing endogenous morphine from the organs and fluids of vertebrates, including bovine brain and adrenal gland, rat heart and adrenal gland, and human heart and urine (for review, Refs. 1-3); invertebrates (4 -6); and parasites (7,8). In mammals, the endogenous morphine synthetic pathway is associated with the dopamine and catecholamine biosynthetic pathway (for review, see Refs.…”

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confidence: 99%

Identification of Morphine-6-glucuronide in Chromaffin Cell Secretory Granules

Goumon

Muller²,

Glattard³

et al. 2006

Journal of Biological Chemistry

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We report for the first time that morphine-6-glucuronide, a highly analgesic morphine-derived molecule, is present in adrenal chromaffin granules and secreted from chromaffin cells upon stimulation. We also demonstrate that phosphatidylethanolamine-binding protein (alternatively named Raf-1 kinase inhibitor protein or RKIP) acts as an endogenous morphine-6-glucuronide-binding protein. An UDPglucuronosyltransferase 2B-like enzyme, described to transform morphine into morphine-6-glucuronide, has been immunodetected in the chromaffin granule matrix, and morphine-6-glucuronide de novo synthesis has been characterized, demonstrating the possible involvement of intragranular UDP-glucuronosyltransferase 2B-like enzyme in morphine-6-glucuronide metabolism. Once secreted into the circulation, morphine-6-glucuronide may mediate several systemic actions (e.g. on immune cells) based on its affinity for -opioid receptors. These activities could be facilitated by phosphatidylethanolamine-binding protein (PEBP), acting as a molecular shield and preventing morphine-6-glucuronide from rapid clearance. Taken together, our data represent an important observation on the role of morphine-6-glucuronide as a new endocrine factor.For 20 years, cerebral endogenous morphine has been isolated and characterized, and its structure has been shown to be identical to morphine from poppy (1, 2). In the 1990s, few groups succeeded in characterizing endogenous morphine from the organs and fluids of vertebrates, including bovine brain and adrenal gland, rat heart and adrenal gland, and human heart and urine (for review, Refs. 1-3); invertebrates (4 -6); and parasites (7,8). In mammals, the endogenous morphine synthetic pathway is associated with the dopamine and catecholamine biosynthetic pathway (for review, see Refs. 1, 3, and 9). Very recently, several crucial steps were reached when Zenk and co-workers (10, 11) demonstrated that morphine can be formed using a multistep biosynthetic route, and Zhu et al. (12) showed that human primary polymorphonuclear cells are able to synthesize morphine. These authors have shown morphine de novo synthesis in human and animal primary and cancer cell cultures.Chromaffin cells are neuroendocrine cells originating from the neural crest and are the predominant cell type in the adrenal medulla (for review, see Ref. 13). These cells possess the catecholamine biosynthetic pathway, leading to dopamine and adrenaline/noradrenaline synthesis (13). Chromaffin secretory granules contain a complex mixture of peptides and proteins that are co-released with catecholamines into the circulation in response to splanchnic nerve stimulation (13). Based on the morphine biosynthetic pathway and on the presence of morphine in bovine and rat adrenal glands (14, 15), rat pheochromocytoma PC-12 cells (10, 16), and eel chromaffin cells (17), we hypothesized that mammalian chromaffin cells might have the capacity to synthesize morphine and that their secretory granules could potentially release this alkaloid into the blood.Several mole...

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“…Sequence analysis indicates striking structural similarities between l 3 and l 3-like receptors, most notably the lack Ascaris suum: ganglia [80], muscle [81], uterus [81] Dracunculus medinensis: whole body extraction [82] Schistosoma mansoni: whole body extraction [82] Homarus americanus: ganglia [83] Vertebrates Human: cell line SH-SY-5Y [84], heart [85], white blood cells [86] of an extended N-terminal glycosylated domain and transmembrane helical domain expressed from exon 1 of the l opioid receptor gene and unique intracellular C-terminal coupling domains [108]. Future structure-function studies will be designed to elucidate the biochemical basis of the selective molecular recognition profiles of these receptors for morphine and morphinan alkaloids.…”

Section: Future Directionsmentioning

confidence: 98%

The Presence of Endogenous Morphine Signaling in Animals

et al. 2008

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Recent empirical findings have contributed valuable mechanistic information in support of a regulated de novo biosynthetic pathway for chemically authentic morphine and related morphinan alkaloids within animal cells. Importantly, we and others have established that endogenously expressed morphine represents a key regulatory molecule effecting local circuit autocrine/paracrine cellular signaling via a novel mu(3) opiate receptor coupled to constitutive nitric oxide production and release. The present report provides an integrated review of the biochemical, pharmacological, and molecular demonstration of mu(3) opiate receptors in historical linkage to the elucidation of mechanisms of endogenous morphine production by animal cells and organ systems. Ongoing research in this exciting area provides a rare window of opportunity to firmly establish essential biochemical linkages between dopamine, a morphine precursor, and animal biosynthetic pathways involved in morphine biosynthesis that have been conserved throughout evolution.

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Ascaris suum, an Intestinal Parasite, Produces Morphine

Cited by 25 publications

References 36 publications

Evidence for the presence of morphine like substance and μ opiate receptor expression in Dicrocoelium dendriticum (Trematoda: Dicrocoeliidae)

Evidence for the presence of morphine like substance and μ opiate receptor expression in Dicrocoelium dendriticum (Trematoda: Dicrocoeliidae)

Identification of Morphine-6-glucuronide in Chromaffin Cell Secretory Granules

The Presence of Endogenous Morphine Signaling in Animals

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