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Zur Physiologie und Pharmakologie von Endorphinen

On the physiology and pharmacology of endorphins

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Summary

Endorphins are peptides with opiate-like action synthesized in various tissues, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) is likely to be a fragment of the peptides α- and β-endorphin, both showing opioid-like actions, as well as of β-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. β-lipotropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulators or even of neurotransmitters. The pharmacological actions of endorphins resemble those of “classical opiates”, both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet.

Zusammenfassung

Die vor wenigen Jahren entdeckten Endorphine sind Peptide mit Opioid-ähnlicher Wirkung, die in verschiedenen Geweben des Organismus, vor allem im Darm und im Zentralnervensystem, synthetisiert werden. Die Entdeckung dieser Substanzgruppe war erst möglich, nachdem Opioid-spezifische Rezeptoren exakt charakterisiert werden konnten und sehr empfindliche Testmethoden für Opioide entwickelt worden waren. Die beiden zuerst entdeckten Endorphine, die Enkephaline, sind Pentapeptide, von denen das met-Enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) offenbar ein Bruchstück der ebenfalls Opioid-ähnliche Wirkung zeigenden Peptide α- und β-Endorphin sowie des in dieser Hinsicht unwirksamen Polypeptids β-Lipotropin ist: Alle diese Peptide enthalten die Sequenz von met-Enkephalin. β-Lipotropin und ACTH entstammen sehr wahrscheinlich einer gemeinsamen Vorstufe. Mindestens die (besonders gut untersuchten) Enkephaline entstehen offensichtlich im Zellkörper und werden von dort zur Nervenendigung transportiert, wo sie freigesetzt werden und vermutlich als Neuromodulatoren oder sogar Neurotransmitter fungieren.

Endorphine zeigen ein ähnliches pharmakologisches Wirkungsspektrum wie “klassische Opiate”, z.B. eine analgetische Wirkung. Endorphine, oder genauer gesagt, die Enkephaline, sind unter anderem an verschiedenen, für die Schmerzperzeption und-transmission „strategisch“ wichtigen Stellen des Zentralnervensystems lokalisiert. Vermutlich spielen sie unter gewissen Bedingungen bei der Regulation der Schmerzperzeption eine Rolle. Eine weitere Bedeutung dieser Substanzen scheint in der Regulation verschiedener neuroendokriner Prozesse zu liegen. Fraglicher ist ihre Signifikanz beim Zustandekommen bestimmter Symptome schizophrener Psychosen. Im Zustand der Opiat-Abhängigkeit konnten bisher keine nennenswerten Veränderungen des Enkephalin-Gehaltes festgestellt werden.

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Kuschinsky, K. Zur Physiologie und Pharmakologie von Endorphinen. Klin Wochenschr 57, 701–710 (1979). https://doi.org/10.1007/BF01477551

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