Endorphins

Endorphins (contracted from endogenous morphine)[1][2] are endogenous opioid neuropeptides and peptide hormones in humans and other animals. They are produced and stored in an area of the brain known as the pituitary gland.

The main function of endorphins is to reduce the communication of pain signals in the body. They may also produce a feeling of euphoria very similar to that produced by other opioids.[3]

History

Opioid peptides in the brain were first discovered in 1973 by investigators at the University of Aberdeen, John Hughes and Hans Kosterlitz. They isolated "enkephalins" (from the Greek εγκέφαλος, cerebrum) from pig brain, identified as Met-enkephalin and Leu-enkephalin.[4][5][6][7] This came after the discovery of a receptor that was proposed to produce the pain-relieving analgesic effects of morphine and other opioids, which led Kosterlitz and Hughes to their discovery of the endogenous opioid ligands.[8] Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of morphine.[7][9]

Rabi Simantov and Solomon H. Snyder isolated morphine-like peptides from calf brain.[10] Eric J. Simon, who independently discovered opioid receptors, would later term these peptides as endorphins.[11] This term was essentially assigned to any peptide that demonstrated morphine-like activity.[12] In 1976, Choh Hao Li and David Chung recorded the sequences of α-, β-, and γ-endorphin isolated from camel pituitary glands for their opioid activity.[13][14] They identified that β-endorphin produced strong analgesic effects.[14] Wilhelm Feldberg and Derek George Smyth in 1977 confirmed this claim, finding β-endorphin to be much stronger than morphine. In addition, they found that it is completely removed from opiate receptors by naloxone, an identified morphine antagonist.[15]

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced morphine,[16][17] which is not a peptide. Opioid peptides are classified based on their precursor propeptide: all endorphins are synthesized from the precursor proopiomelanocortin (POMC), encoded by proenkephalin A, and dynorphins encoded by pre-dynorphin.[18][19]

Etymology

The word endorphin is derived from ἔνδον / Greek: éndon meaning "within" (endogenous, ἐνδογενής / Greek: endogenes, "proceeding from within"), and morphine, from Morpheus (Ancient Greek: Μορφεύς, romanized: Morpheús), the god of dreams in the Greek mythology. Thus, endorphin is a contraction of 'endo(genous) (mo)rphin' (morphin being the old spelling of morphine).

Types

The class of endorphins consists of three endogenous opioid peptides: α-endorphin, β-endorphin, and γ-endorphin.[20] The endorphins are all synthesized from the precursor protein, proopiomelanocortin, and all contain a Met-enkephalin motif at their N-terminus: Tyr-Gly-Gly-Phe-Met.[21] α-endorphin and γ-endorphin result from proteolytic cleavage of β-endorphin between the Thr(16)-Leu(17) residues and Leu(17)-Phe(18) respectively.[22] α-endorphin has the shortest sequence, and β-endorphin has the longest sequence.

α-endorphin and γ-endorphin are primarily found in the anterior and intermediate pituitary.[23] While β-endorphin is studied for its opioid activity, α-endorphin and γ-endorphin both lack affinity for opiate receptors and thus do not affect the body in the same way that β-endorphin does. Some studies have characterized α-endorphin activity as similar to that of psychostimulants and γ-endorphin activity to that neuroleptics separately.[23]

Name Sequence Reference
α-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH [24][9]
β-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu [25][26]
γ-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH [24][9]

Synthesis

Endorphin precursors are primarily produced in the pituitary gland.[27][28][29] All three types of endorphins are fragments of the precursor protein proopiomelanocortin (POMC). At the trans-Golgi network, POMC binds to a membrane-bound protein, carboxypeptidase E (CPE).[30] CPE facilitates POMC transport into immature budding vesicles.[31] In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and beta-lipotropin (β-LPH).[30] β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including α-endorphin, β-endorphin, and γ-endorphin.[26][32][33] Peptide convertase 2 (PC2) is responsible for cleaving β-LPH into β-endorphin and γ-lipotropin.[9] Formation of α-endorphin and γ-endorphin results from proteolytic cleavage of β-endorphin.[22]

Regulation

Noradrenaline has been shown to increase endorphins production within inflammatory tissues, resulting in an analgesic effect;[34] the stimulation of sympathetic nerves by electro-acupuncture is believed to be the cause of its analgesic effects.[35]

Mechanism of action

Endorphins are released from the pituitary gland, typically in response to pain, and can act in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the PNS, β-endorphin is the primary endorphin released from the pituitary gland. Endorphins inhibit transmission of pain signals by binding μ-receptors of peripheral nerves, which block their release of neurotransmitter substance P. The mechanism in the CNS is similar but works by blocking a different neurotransmitter: gamma-aminobutyric acid (GABA). In turn, inhibition of GABA increases the production and release of dopamine, a neurotransmitter associated with reward learning.[25][36]

Functions

Endorphins play a major role in the body's inhibitory response to pain. Research has demonstrated that meditation by trained individuals can be used to trigger endorphin release.[37] Laughter may also stimulate endorphin production and elevate one's pain threshold.[38]

Endorphin production can be triggered by vigorous aerobic exercise. The release of β-endorphin has been postulated to contribute to the phenomenon known as a "runner's high."[39][40] However, several studies have supported the hypothesis that the runner's high is due to the release of endocannabinoids rather than that of endorphins.[41] Endorphins may contribute to the positive effect of exercise on anxiety and depression.[42] The same phenomenon may also play a role in exercise addiction. Regular intense exercise may cause the brain to downregulate the production of endorphins in periods of rest to maintain homeostasis, causing a person to exercise more intensely in order to receive the same feeling.[43]

References

  1. Stefano GB, Ptáček R, Kuželová H, Kream RM (1515). "Endogenous morphine: up-to-date review 2011" (PDF). Folia Biologica. 58 (2): 49–56. PMID 22578954. Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. ... The apparently serendipitous finding of an opiate alkaloid-sensitive, opioid peptide-insensitive, µ3 opiate receptor subtype expressed by invertebrate immunocytes, human blood monocytes, macrophage cell lines, and human blood granulocytes provided compelling validating evidence for an autonomous role of endogenous morphine as a biologically important cellular signalling molecule (Stefano et al., 1993; Cruciani et al., 1994; Stefano and Scharrer, 1994; Makman et al., 1995). ... Human white blood cells have the ability to make and release morphine
  2. "μ receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. 15 March 2017. Retrieved 28 December 2017. Comments: β-Endorphin is the highest potency endogenous ligand ... Morphine occurs endogenously 117. {{cite web}}: External link in |quote= (help)
  3. "Is there a link between exercise and happiness?". 22 June 2009. Archived from the original on 14 August 2014. Retrieved 18 September 2014.
  4. "Role of endorphins discovered". PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1 January 1998. Retrieved 15 October 2008.
  5. Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (December 1975). "Identification of two related pentapeptides from the brain with potent opiate agonist activity". Nature. 258 (5536): 577–80. Bibcode:1975Natur.258..577H. doi:10.1038/258577a0. PMID 1207728. S2CID 95411.
  6. Berezniuk, Iryna; Fricker, Lloyd D. (2011), Pasternak, Gavril W. (ed.), "Endogenous Opioids", The Opiate Receptors, The Receptors, Totowa, NJ: Humana Press, pp. 93–120, doi:10.1007/978-1-60761-993-2_5, ISBN 978-1-60761-993-2, retrieved 25 October 2020
  7. Corbett, Alistair D; Henderson, Graeme; McKnight, Alexander T; Paterson, Stewart J (January 2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail". British Journal of Pharmacology. 147 (Suppl 1): S153–S162. doi:10.1038/sj.bjp.0706435. ISSN 0007-1188. PMC 1760732. PMID 16402099.
  8. Corbett, Alistair D; Henderson, Graeme; McKnight, Alexander T; Paterson, Stewart J (January 2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail: Opioids and opioid peptides". British Journal of Pharmacology. 147 (S1): S153–S162. doi:10.1038/sj.bjp.0706435. PMC 1760732. PMID 16402099.
  9. Purves D (4 July 2018). Neuroscience (Sixth ed.). New York. ISBN 978-1-60535-380-7. OCLC 990257568.
  10. Simantov R, Snyder SH (July 1976). "Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor". Proceedings of the National Academy of Sciences of the United States of America. 73 (7): 2515–9. Bibcode:1976PNAS...73.2515S. doi:10.1073/pnas.73.7.2515. PMC 430630. PMID 1065904.
  11. Goldstein A, Lowery PJ (September 1975). "Effect of the opiate antagonist naloxone on body temperature in rats". Life Sciences. 17 (6): 927–31. doi:10.1016/0024-3205(75)90445-2. PMID 1195988.
  12. McLaughlin, Patricia J.; Zagon, Ian S. (2013), "POMC-Derived Opioid Peptides", Handbook of Biologically Active Peptides, Elsevier, pp. 1592–1595, doi:10.1016/b978-0-12-385095-9.00217-7, ISBN 978-0-12-385095-9, retrieved 9 November 2020
  13. Li, C. H.; Chung, D. (April 1976). "Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands". Proceedings of the National Academy of Sciences of the United States of America. 73 (4): 1145–1148. Bibcode:1976PNAS...73.1145L. doi:10.1073/pnas.73.4.1145. ISSN 0027-8424. PMC 430217. PMID 1063395.
  14. Smyth, D G (May 2016). "60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective". Journal of Molecular Endocrinology. 56 (4): T13–T25. doi:10.1530/JME-16-0033. ISSN 0952-5041. PMID 26903509.
  15. FELDBERG, W.; SMYTH, D.G. (July 1977). "C-Fragment of Lipotropin-An Endogenous Potent Analgesic Peptide". British Journal of Pharmacology. 60 (3): 445–453. doi:10.1111/j.1476-5381.1977.tb07521.x. ISSN 0007-1188. PMC 1667279. PMID 560894.
  16. Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH (September 2004). "Endogenous formation of morphine in human cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (39): 14091–6. Bibcode:2004PNAS..10114091P. doi:10.1073/pnas.0405430101. PMC 521124. PMID 15383669.
  17. Kream RM, Stefano GB (October 2006). "De novo biosynthesis of morphine in animal cells: an evidence-based model". Medical Science Monitor. 12 (10): RA207-19. PMID 17006413.
  18. Purves D (4 July 2018). Neuroscience (Sixth ed.). New York. ISBN 978-1-60535-380-7. OCLC 990257568.
  19. Stein, Christoph (14 January 2016). "Opioid Receptors". Annual Review of Medicine. 67 (1): 433–451. doi:10.1146/annurev-med-062613-093100. ISSN 0066-4219. PMID 26332001.
  20. Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R (February 2012). "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins". Future Medicinal Chemistry. 4 (2): 205–26. doi:10.4155/fmc.11.195. PMC 3306179. PMID 22300099.
  21. Purves D (4 July 2018). Neuroscience (Sixth ed.). New York. ISBN 978-1-60535-380-7. OCLC 990257568.
  22. Burbach, J.Peter H. (January 1984). "Action of proteolytic enzymes on lipotropins and endorphins: Biosynthesis, biotransformation and fate". Pharmacology & Therapeutics. 24 (3): 321–354. doi:10.1016/0163-7258(84)90008-1. hdl:1874/25178. ISSN 0163-7258. PMID 6087385.
  23. Wiegant, Victor M.; Ronken, Eric; Kovács, Gabor; De Wied, David (1992), "Chapter 29 Endorphins and schizophrenia", Progress in Brain Research, Elsevier, vol. 93, pp. 433–453, doi:10.1016/s0079-6123(08)64588-4, ISBN 978-0-444-89538-7, retrieved 9 November 2020
  24. Ling N, Burgus R, Guillemin R (November 1976). "Isolation, primary structure, and synthesis of alpha-endorphin and gamma-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity". Proceedings of the National Academy of Sciences of the United States of America. 73 (11): 3942–6. Bibcode:1976PNAS...73.3942L. doi:10.1073/pnas.73.11.3942. PMC 431275. PMID 1069261.
  25. Chaudhry SR, Bhimji SS (2018). Biochemistry, Endorphin. StatPearls. StatPearls Publishing. PMID 29262177. Retrieved 20 February 2019.
  26. Ambinder RF, Schuster MM (November 1979). "Endorphins: new gut peptides with a familiar face". Gastroenterology. 77 (5): 1132–40. doi:10.1016/S0016-5085(79)80089-X. PMID 226450.
  27. Burbach, J.Peter H. (January 1984). "Action of proteolytic enzymes on lipotropins and endorphins: Biosynthesis, biotransformation and fate". Pharmacology & Therapeutics. 24 (3): 321–354. doi:10.1016/0163-7258(84)90008-1. hdl:1874/25178. ISSN 0163-7258. PMID 6087385.
  28. Mousa, Shaaban A.; Shakibaei, Mehdi; Sitte, Nicolle; Schäfer, Michael; Stein, Christoph (1 March 2004). "Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain". Endocrinology. 145 (3): 1331–1341. doi:10.1210/en.2003-1287. ISSN 0013-7227. PMID 14630714.
  29. Takahashi, Akiyoshi; Mizusawa, Kanta (2013). "Posttranslational Modifications of Proopiomelanocortin in Vertebrates and Their Biological Significance". Frontiers in Endocrinology. 4: 143. doi:10.3389/fendo.2013.00143. ISSN 1664-2392. PMC 3797980. PMID 24146662. S2CID 18975702.
  30. Mousa, Shaaban A.; Shakibaei, Mehdi; Sitte, Nicolle; Schäfer, Michael; Stein, Christoph (1 March 2004). "Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain". Endocrinology. 145 (3): 1331–1341. doi:10.1210/en.2003-1287. ISSN 0013-7227. PMID 14630714.
  31. Loh, Y. Peng; Kim, Taeyoon; Rodriguez, Yazmin M.; Cawley, Niamh X. (2004). "Secretory Granule Biogenesis and Neuropeptide Sorting to the Regulated Secretory Pathway in Neuroendocrine Cells". Journal of Molecular Neuroscience. 22 (1–2): 63–72. doi:10.1385/jmn:22:1-2:63. ISSN 0895-8696. PMID 14742911. S2CID 30140731.
  32. Crine P, Gianoulakis C, Seidah NG, Gossard F, Pezalla PD, Lis M, Chrétien M (October 1978). "Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia". Proceedings of the National Academy of Sciences of the United States of America. 75 (10): 4719–23. Bibcode:1978PNAS...75.4719C. doi:10.1073/pnas.75.10.4719. PMC 336191. PMID 216997.
  33. Goldstein A (September 1976). "Opioid peptides endorphins in pituitary and brain". Science. 193 (4258): 1081–6. Bibcode:1976Sci...193.1081G. doi:10.1126/science.959823. PMID 959823.
  34. https://pubmed.ncbi.nlm.nih.gov/15245482/
  35. https://www.sciencedirect.com/topics/medicine-and-dentistry/electroacupuncture
  36. Sprouse-Blum AS, Smith G, Sugai D, Parsa FD (March 2010). "Understanding endorphins and their importance in pain management". Hawaii Medical Journal. 69 (3): 70–1. PMC 3104618. PMID 20397507.
  37. Dfarhud D, Malmir M, Khanahmadi M (November 2014). "Happiness & Health: The Biological Factors- Systematic Review Article". Iranian Journal of Public Health. 43 (11): 1468–77. PMC 4449495. PMID 26060713.
  38. Dunbar RI, Baron R, Frangou A, Pearce E, van Leeuwen EJ, Stow J, Partridge G, MacDonald I, Barra V, van Vugt M (March 2012). "Social laughter is correlated with an elevated pain threshold". Proceedings: Biological Sciences. 279 (1731): 1161–7. doi:10.1098/rspb.2011.1373. PMC 3267132. PMID 21920973.
  39. Boecker, Henning; Sprenger, Till; Spilker, Mary E.; Henriksen, Gjermund; Koppenhoefer, Marcus; Wagner, Klaus J.; Valet, Michael; Berthele, Achim; Tolle, Thomas R. (1 November 2008). "The Runner's High: Opioidergic Mechanisms in the Human Brain". Cerebral Cortex. 18 (11): 2523–2531. doi:10.1093/cercor/bhn013. ISSN 1047-3211. PMID 18296435.
  40. Kolata G (27 March 2008). "Yes, Running Can Make You High". The New York Times. ISSN 0362-4331. Retrieved 26 May 2016.
  41. Reynolds, Gretchen (10 March 2021). "Getting to the Bottom of the Runner's High". The New York Times. ISSN 0362-4331. Retrieved 16 March 2021.
  42. Anderson E, Shivakumar G (23 April 2013). "Effects of exercise and physical activity on anxiety". Frontiers in Psychiatry. 4: 27. doi:10.3389/fpsyt.2013.00027. PMC 3632802. PMID 23630504.
  43. Freimuth M, Moniz S, Kim SR (October 2011). "Clarifying exercise addiction: differential diagnosis, co-occurring disorders, and phases of addiction". International Journal of Environmental Research and Public Health. 8 (10): 4069–81. doi:10.3390/ijerph8104069. PMC 3210598. PMID 22073029.
  • Endorphins at the US National Library of Medicine Medical Subject Headings (MeSH)
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.