Editing Endorphins (section)

== History ==
[[Opioid peptide]]s in the brain were first discovered in 1973 by investigators at the University of Aberdeen, [[John Hughes (neuroscientist)|John Hughes]] and [[Hans Kosterlitz]]. They isolated "[[enkephalin]]s" (from the [[Greek language|Greek]] {{lang|el|εγκέφαλος}}) from [[pig]] [[brain]], identified as Met-enkephalin and Leu-enkephalin.<ref name="pbs.org">{{cite web|date=1 January 1998|title=Role of endorphins discovered|url=https://www.pbs.org/wgbh/aso/databank/entries/dh75en.html|access-date=15 October 2008|work=PBS Online: A Science Odyssey: People and Discoveries|publisher=Public Broadcasting System}}</ref><ref>{{cite journal | vauthors = Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR | title = Identification of two related pentapeptides from the brain with potent opiate agonist activity | journal = Nature | volume = 258 | issue = 5536 | pages = 577–580 | date = December 1975 | pmid = 1207728 | doi = 10.1038/258577a0 | bibcode = 1975Natur.258..577H }}</ref><ref>{{cite book | vauthors = Berezniuk I, Fricker LD | chapter = Endogenous Opioids|date=2011 | title = The Opiate Receptors|pages=93–120 | veditors = Pasternak GW|series=The Receptors|place=Totowa, NJ | publisher=Humana Press|language=en |doi=10.1007/978-1-60761-993-2_5 |isbn=978-1-60761-993-2 }}</ref><ref name="Corbett2006">{{cite journal | vauthors = Corbett AD, Henderson G, McKnight AT, Paterson SJ | title = 75 years of opioid research: the exciting but vain quest for the Holy Grail | journal = British Journal of Pharmacology | volume = 147 | issue = Suppl 1 | pages = S153–S162 | date = January 2006 | pmid = 16402099 | pmc = 1760732 | doi = 10.1038/sj.bjp.0706435 }}</ref>  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.<ref name="Corbett2006" /> Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of [[morphine]].<ref name="Corbett2006" /><ref name="Purves2018">{{Cite book |url=https://books.google.com/books?id=4xoGDQEACAAJ |title=Neuroscience|date=2018 | vauthors = Purves D, Fitzpatrick D, Augustine GJ |isbn=9781605353807 |location=New York | publisher = Sunderland |oclc=990257568|edition=6th }}</ref>

Rabi Simantov and [[Solomon H. Snyder]] isolated morphine-like peptides from [[calf (animal)|calf]] brain.<ref>{{cite journal | vauthors = Simantov R, Snyder SH | title = Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 7 | pages = 2515–2519 | date = July 1976 | pmid = 1065904 | pmc = 430630 | doi = 10.1073/pnas.73.7.2515 | doi-access = free | bibcode = 1976PNAS...73.2515S }}</ref> [[Eric J. Simon]], who independently discovered opioid receptors, later termed these peptides as endorphins.<ref name="pmid1195988">{{cite journal | vauthors = Goldstein A, Lowery PJ | title = Effect of the opiate antagonist naloxone on body temperature in rats | journal = Life Sciences | volume = 17 | issue = 6 | pages = 927–931 | date = September 1975 | pmid = 1195988 | doi = 10.1016/0024-3205(75)90445-2 }}</ref> This term was essentially assigned to any peptide that demonstrated morphine-like activity.<ref name="McLaughlin2020">{{cite book | vauthors = McLaughlin PJ, Zagon IS | chapter = POMC-Derived Opioid Peptides|date=2013 | title = Handbook of Biologically Active Peptides|pages=1592–1595|publisher=Elsevier |language=en|doi=10.1016/b978-0-12-385095-9.00217-7|isbn=978-0-12-385095-9 }}</ref> 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.<ref>{{cite journal | vauthors = Li CH, Chung D | title = Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 4 | pages = 1145–1148 | date = April 1976 | pmid = 1063395 | pmc = 430217 | doi = 10.1073/pnas.73.4.1145 | doi-access = free | bibcode = 1976PNAS...73.1145L }}</ref><ref name=":6">{{cite journal | vauthors = Smyth DG | title = 60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective | journal = Journal of Molecular Endocrinology | volume = 56 | issue = 4 | pages = T13–T25 | date = May 2016 | pmid = 26903509 | doi = 10.1530/JME-16-0033 | doi-access = free }}</ref> Li determined that β-endorphin produced strong analgesic effects.<ref>{{cite journal | vauthors = Loh HH, Tseng LF, Wei E, Li CH | title = beta-endorphin is a potent analgesic agent | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 8 | pages = 2895–2898 | date = August 1976 | pmid = 8780 | pmc = 430793 | doi = 10.1073/pnas.73.8.2895 | doi-access = free | bibcode = 1976PNAS...73.2895L }}</ref> [[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]].<ref>{{cite journal | vauthors = Feldberg W, Smyth DG | title = C-fragment of lipotropin--an endogenous potent analgesic peptide | journal = British Journal of Pharmacology | volume = 60 | issue = 3 | pages = 445–453 | date = July 1977 | pmid = 560894 | pmc = 1667279 | doi = 10.1111/j.1476-5381.1977.tb07521.x }}</ref>

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced true [[morphine]],<ref name="pmid15383669">{{cite journal | vauthors = Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH | title = Endogenous formation of morphine in human cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 39 | pages = 14091–14096 | date = September 2004 | pmid = 15383669 | pmc = 521124 | doi = 10.1073/pnas.0405430101 | doi-access = free | bibcode = 2004PNAS..10114091P }}</ref><ref name="pmid17006413">{{cite journal | vauthors = Kream RM, Stefano GB | title = De novo biosynthesis of morphine in animal cells: an evidence-based model | journal = Medical Science Monitor | volume = 12 | issue = 10 | pages = RA207–RA219 | date = October 2006 | pmid = 17006413 | url = https://medscimonit.com/abstract/index/idArt/459203 }}</ref> 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.<ref name="Purves2018" /><ref>{{cite journal | vauthors = Stein C | title = Opioid Receptors | journal = Annual Review of Medicine | volume = 67 | issue = 1 | pages = 433–451 | date = 2016-01-14 | pmid = 26332001 | doi = 10.1146/annurev-med-062613-093100 | doi-access = free }}</ref>