Wikipedia

Endorphins

(Redirected from Endorphin)

For other uses, see Endorphins (disambiguation).

Endorphins (contracted from endogenous morphine)[1][2][3] are peptides produced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in the pituitary gland of the brain. Endorphins are endogenous painkillers often produced in the brain and adrenal medulla during physical exercise or orgasm and inhibit pain, muscle cramps, and relieve stress.[4][5][6][7]

Chemical Structure of Endorphin
Physical activity and exercise release the most endorphins.
Cocoa powder helps most among the edible substances to produce endorphins in human body.

History

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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.[8][9][10][11] 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.[11] Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of morphine.[11][12]

Rabi Simantov and Solomon H. Snyder isolated morphine-like peptides from calf brain.[13] Eric J. Simon, who independently discovered opioid receptors, later termed these peptides as endorphins.[14] This term was essentially assigned to any peptide that demonstrated morphine-like activity.[15] 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.[16][17] Li determined that β-endorphin produced strong analgesic effects.[18] Wilhelm Feldberg and Derek George Smyth in 1977 confirmed this, finding β-endorphin to be more potent than morphine. They also confirmed that its effects were reversed by naloxone, an opioid antagonist.[19]

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced morphine,[20][21] 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.[12][22]

Etymology

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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

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The class of endorphins consists of three endogenous opioid peptides: α-endorphin, β-endorphin, and γ-endorphin.[23] 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.[12] 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.[24] 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.[25] 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 of neuroleptics separately.[25]

Name Sequence Reference
α-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH [26][12]
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 [27][28]
γ-endorphin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH [26][12]

Synthesis

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Endorphin precursors are primarily produced in the pituitary gland.[29][30][31] 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).[32] CPE facilitates POMC transport into immature budding vesicles.[33] In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and beta-lipotropin (β-LPH).[32] β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including α-endorphin, β-endorphin, and γ-endorphin.[28][34][35] Peptide convertase 2 (PC2) is responsible for cleaving β-LPH into β-endorphin and γ-lipotropin.[12] Formation of α-endorphin and γ-endorphin results from proteolytic cleavage of β-endorphin.[24]

Regulation

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Noradrenaline has been shown to increase endorphins production within inflammatory tissues, resulting in an analgesic effect;[36] the stimulation of sympathetic nerves by electro-acupuncture is believed to be the cause of its analgesic effects.[37]

Mechanism of action

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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.[27][38]

Functions

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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.[39][failed verification] Laughter may also stimulate endorphin production and elevate one's pain threshold.[40]

Endorphin production can be triggered by vigorous aerobic exercise. The release of β-endorphin has been postulated to contribute to the phenomenon known as "runner's high".[41][42] However, several studies have supported the hypothesis that the runner's high is due to the release of endocannabinoids rather than that of endorphins.[43] Endorphins may contribute to the positive effect of exercise on anxiety and depression.[44] 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.[45]

See also

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References

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  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.
  3. ^ 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): 14091–14096. Bibcode:2004PNAS..10114091P. doi:10.1073/pnas.0405430101. PMC 521124. PMID 15383669.
  4. ^ Pilozzi A, Carro C, Huang X (December 2020). "Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism". International Journal of Molecular Sciences. 22 (1): 338. doi:10.3390/ijms22010338. PMC 7796446. PMID 33396962.
  5. ^ Howlett TA, Tomlin S, Ngahfoong L, Rees LH, Bullen BA, Skrinar GS, McArthur JW (June 1984). "Release of beta endorphin and met-enkephalin during exercise in normal women: response to training". British Medical Journal. 288 (6435): 1950–1952. doi:10.1136/bmj.288.6435.1950. PMC 1442192. PMID 6329401.
  6. ^ Goldfarb AH, Jamurtas AZ (July 1997). "Beta-endorphin response to exercise. An update". Sports Medicine. 24 (1): 8–16. doi:10.2165/00007256-199724010-00002. PMID 9257407. S2CID 72824962.
  7. ^ "Endorphins: What They Are and How to Boost Them". Cleveland Clinic. Retrieved 25 March 2023.
  8. ^ "Role of endorphins discovered". PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1 January 1998. Retrieved 15 October 2008.
  9. ^ 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): 577–580. Bibcode:1975Natur.258..577H. doi:10.1038/258577a0. PMID 1207728. S2CID 95411.
  10. ^ Berezniuk I, Fricker LD (2011). "Endogenous Opioids". In Pasternak GW (ed.). 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.
  11. ^ a b c Corbett AD, Henderson G, McKnight AT, Paterson SJ (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. PMC 1760732. PMID 16402099.
  12. ^ a b c d e f Purves D, Fitzpatrick D, Augustine GJ (2018). Neuroscience (6th ed.). New York: Sunderland. ISBN 9781605353807. OCLC 990257568.
  13. ^ 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): 2515–2519. Bibcode:1976PNAS...73.2515S. doi:10.1073/pnas.73.7.2515. PMC 430630. PMID 1065904.
  14. ^ Goldstein A, Lowery PJ (September 1975). "Effect of the opiate antagonist naloxone on body temperature in rats". Life Sciences. 17 (6): 927–931. doi:10.1016/0024-3205(75)90445-2. PMID 1195988.
  15. ^ McLaughlin PJ, Zagon IS (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.
  16. ^ Li CH, 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. PMC 430217. PMID 1063395.
  17. ^ Smyth DG (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. PMID 26903509.
  18. ^ Loh HH, Tseng LF, Wei E, Li CH (August 1976). "beta-endorphin is a potent analgesic agent". Proceedings of the National Academy of Sciences of the United States of America. 73 (8): 2895–2898. Bibcode:1976PNAS...73.2895L. doi:10.1073/pnas.73.8.2895. PMC 430793. PMID 8780.
  19. ^ Feldberg W, Smyth DG (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. PMC 1667279. PMID 560894.
  20. ^ 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): 14091–14096. Bibcode:2004PNAS..10114091P. doi:10.1073/pnas.0405430101. PMC 521124. PMID 15383669.
  21. ^ Kream RM, Stefano GB (October 2006). "De novo biosynthesis of morphine in animal cells: an evidence-based model". Medical Science Monitor. 12 (10): RA207–RA219. PMID 17006413.
  22. ^ Stein C (14 January 2016). "Opioid Receptors". Annual Review of Medicine. 67 (1): 433–451. doi:10.1146/annurev-med-062613-093100. PMID 26332001.
  23. ^ 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): 205–226. doi:10.4155/fmc.11.195. PMC 3306179. PMID 22300099.
  24. ^ a b Burbach JP (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. PMID 6087385.
  25. ^ a b Wiegant VM, Ronken E, Kovács G, De Wied D (1992). Endorphins and schizophrenia. Progress in Brain Research. Vol. 93. pp. 433–53. PMID 1480761.
  26. ^ a b 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): 3942–3946. Bibcode:1976PNAS...73.3942L. doi:10.1073/pnas.73.11.3942. PMC 431275. PMID 1069261.
  27. ^ a b Chaudhry SR, Bhimji SS (2018). "Biochemistry, Endorphin". StatPearls. StatPearls Publishing. PMID 29262177. Retrieved 20 February 2019.
  28. ^ a b Ambinder RF, Schuster MM (November 1979). "Endorphins: new gut peptides with a familiar face". Gastroenterology. 77 (5): 1132–1140. doi:10.1016/S0016-5085(79)80089-X. PMID 226450.
  29. ^ Burbach JP (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. PMID 6087385.
  30. ^ Mousa SA, Shakibaei M, Sitte N, Schäfer M, Stein C (March 2004). "Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain". Endocrinology. 145 (3): 1331–1341. doi:10.1210/en.2003-1287. PMID 14630714.
  31. ^ Takahashi A, Mizusawa K (October 2013). "Posttranslational modifications of proopiomelanocortin in vertebrates and their biological significance". Frontiers in Endocrinology. 4: 143. doi:10.3389/fendo.2013.00143. PMC 3797980. PMID 24146662. S2CID 18975702.
  32. ^ a b Mousa SA, Shakibaei M, Sitte N, Schäfer M, Stein C (March 2004). "Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain". Endocrinology. 145 (3): 1331–1341. doi:10.1210/en.2003-1287. PMID 14630714.
  33. ^ Loh YP, Kim T, Rodriguez YM, Cawley NX (2004). "Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells". Journal of Molecular Neuroscience. 22 (1–2): 63–71. doi:10.1385/jmn:22:1-2:63. PMID 14742911. S2CID 30140731.
  34. ^ 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): 4719–4723. Bibcode:1978PNAS...75.4719C. doi:10.1073/pnas.75.10.4719. PMC 336191. PMID 216997.
  35. ^ Goldstein A (September 1976). "Opioid peptides endorphins in pituitary and brain". Science. 193 (4258): 1081–1086. Bibcode:1976Sci...193.1081G. doi:10.1126/science.959823. PMID 959823.
  36. ^ Binder W, Mousa SA, Sitte N, Kaiser M, Stein C, Schäfer M (July 2004). "Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue". The European Journal of Neuroscience. 20 (1): 92–100. doi:10.1111/j.1460-9568.2004.03459.x. PMID 15245482. S2CID 33125103.
  37. ^ "Electroacupuncture - an overview | ScienceDirect Topics".
  38. ^ Sprouse-Blum AS, Smith G, Sugai D, Parsa FD (March 2010). "Understanding endorphins and their importance in pain management". Hawaii Medical Journal. 69 (3): 70–71. PMC 3104618. PMID 20397507.
  39. ^ Dfarhud D, Malmir M, Khanahmadi M (November 2014). "Happiness & Health: The Biological Factors- Systematic Review Article". Iranian Journal of Public Health. 43 (11): 1468–1477. PMC 4449495. PMID 26060713.
  40. ^ Dunbar RI, Baron R, Frangou A, Pearce E, van Leeuwen EJ, Stow J, et al. (March 2012). "Social laughter is correlated with an elevated pain threshold". Proceedings. Biological Sciences. 279 (1731): 1161–1167. doi:10.1098/rspb.2011.1373. PMC 3267132. PMID 21920973.
  41. ^ Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, et al. (November 2008). "The runner's high: opioidergic mechanisms in the human brain". Cerebral Cortex. 18 (11): 2523–2531. doi:10.1093/cercor/bhn013. PMID 18296435.
  42. ^ Kolata G (27 March 2008). "Yes, Running Can Make You High". The New York Times. ISSN 0362-4331. Retrieved 26 May 2016.
  43. ^ Reynolds G (10 March 2021). "Getting to the Bottom of the Runner's High". The New York Times. ISSN 0362-4331. Retrieved 16 March 2021.
  44. ^ 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.
  45. ^ 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): 4069–4081. doi:10.3390/ijerph8104069. PMC 3210598. PMID 22073029.
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