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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

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      Comparison of beta-endorphin and CGRP levels before and after treatment for severe schizophrenia

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          Abstract

          Objectives

          Links between endorphins and dopaminergic transmission have not been fully explored in schizophrenia. Both endorphins excess and deficiency were postulated. CGRP is probably involved in dopaminergic transmission. The aim of this study was the evaluation of beta-endorphin (BE) and CGRP blood concentrations before and after treatment of severe schizophrenia.

          Methods

          Seventy patients treated with various antipsychotics, with severe symptoms of schizophrenia (51 with positive symptoms, 19 with negative symptoms), 15 first-degree relatives, and 44 healthy controls were included in the study. BE and CGRP blood concentrations were measured during patients severe schizophrenia and in their stable mental state after treatment. The results were compared with relatives and controls.

          Results

          BE and CGRP concentrations in patients with negative symptoms were higher than in relatives and in controls. BE levels in patients with positive symptoms were lower than in patients with negative symptoms ( P<0.0000) and controls ( P<0.0006). No significant changes in CGRP concentration were found in patient samples. CGRP levels in these samples were independent of treatment, but they were significantly higher than in relatives and controls. After the treatment, BE level decreased in patients with negative symptoms ( P<0.0001) and increased in patients with positive symptoms ( P<0.0000). No differences in BE concentration between patients in stable mental state, their relatives, and controls were found.

          Conclusion

          Effective antipsychotic treatment results in “normalization” of BE level. Specific changes in BE concentration could be involved in dopaminergic transmission and related to some symptoms of schizophrenia.

          Most cited references32

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          Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors.

          Calcitonin generelated peptide (CGRP) is a neuropeptide discovered by a molecular approach over 10 years ago. More recently, islet amyloid polypeptide or amylin, and adrenomedullin were isolated from human insulinoma and pheochromocytoma respectively, and revealed between 25 and 50% sequence homology with CGRP. This review discusses findings on the anatomical distributions of CGRP mRNA, CGRP-like immunoreactivity and receptors in the central nervous system, as well as the potential physiological roles for CGRP. The anatomical distribution and biological activities of amylin and adrenomedullin are also presented. Based upon the differential biological activity of various CGRP analogs, the CGRP receptors have been classified in two major classes, namely the CGRP1 and CGRP2 subtypes. A third subtype has also been proposed (e.g. in the nucleus accumbens) as it does not share the pharmacological properties of the other two classes. The anatomical distribution and the pharmacological characteristics of amylin binding sites in the rat brain are different from those reported for CGRP but share several similarities with the salmon calcitonin receptors. The receptors identified thus far for CGRP and related peptides belong to the G protein-coupled receptor superfamily. Indeed, modulation of adenylate cyclase activity following receptor activation has been reported for CGRP, amylin and adrenomedullin. Furthermore, the binding affinity of CGRP and related peptides is modulated by nucleotides such as GTP. The cloning of various calcitonin and most recently of CGRP1 and adrenomedullin receptors was reported and revealed structural similarities but also significant differences to other members of the G protein-coupled receptors. They may thus form a new subfamily. The cloning of the amylin receptor(s) as well as of the other putative CGRP receptor subtype(s) are still awaited. Finally, a broad variety of biological activities has been described for CGRP-like peptides. These include vasodilation, nociception, glucose uptake and the stimulation of glycolysis in skeletal muscles. These effects may thus suggest their potential role and therapeutic applications in migraine, subarachnoid haemorrhage, diabetes and pain-related mechanisms, among other disorders.
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            Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness.

            The endogenous morphinomimetic brain peptides Met5-enkephalin and alpha-, beta-, and gamma-endorphins have been evaluated in rats after intracerebrospinal fluid injection. beta-Endorphin produces marked, prolonged muscular rigidity and immobility similar to a catatonic state, counteracted by the opiate antagonist naloxone; this effect occurs at molar doses 1/100 to 1/400 that at which the other peptides or morphine block the response to painful stimuli. All peptides evoked dose-related, naloxone-reversible, wet-dog shakes in rats that had not been exposed to drugs. beta-Endorphin produced hypothermia, whereas gamma-endorphin produced hyperthermia. Such potent and divergent responses to naturally occurring subtances suggest that alterations in their homeostatic regulation could have etiological significance in mental illness.
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              Endogenous morphine and its metabolites in mammals: history, synthesis, localization and perspectives.

              Morphine derived from Papaver somniferum is commonly used as an analgesic compound for pain relief. It is now accepted that endogenous morphine, structurally identical to vegetal morphine-alkaloid, is synthesized by mammalian cells from dopamine. Morphine binds mu opioid receptor and induces antinociceptive effects. However, the exact role of these compounds is a matter of debate although different links with infection, sepsis, inflammation, as well as major neurological pathologies (Parkinson's disease, schizophrenia) have been proposed. The present review describes endogenous morphine and morphine derivative discovery, synthesis, localization and potential implications in physiological and pathological processes. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2016
                15 April 2016
                : 12
                : 863-868
                Affiliations
                [1 ]Department of Affective and Psychotic Disorders, Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland
                [2 ]Department of Geriatrics, Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland
                Author notes
                Correspondence: Małgorzata Urban-Kowalczyk, Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechosłowacka 8/10, 92-216 Lodz, Poland, Tel +48 42 675 7371, Fax +48 42 675 7403, Email malgorzata.urban1@ 123456wp.pl
                Article
                ndt-12-863
                10.2147/NDT.S101647
                4841412
                27143887
                f5c52f9c-657c-483a-aac4-43291e17cbf3
                © 2016 Urban-Kowalczyk et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Neurology
                schizophrenia,negative symptoms,neuroleptics,β-endorphin,cgrp
                Neurology
                schizophrenia, negative symptoms, neuroleptics, β-endorphin, cgrp

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