Endorphins (contracted from "endogenous morphine"[note 1]) are endogenous opioid neuropeptides and peptide hormones in humans and other animals. They are produced by the central nervous system and the pituitary gland. The term "endorphins" implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean "a morphine-like substance originating from within the body". The class of endorphins includes three compounds—α-endorphin (alpha endorphins), β-endorphin (beta endorphins), and γ-endorphin (gamma endorphins)—which preferentially bind to μ-opioid receptors. The principal function of endorphins is to inhibit the communication of pain signals; they may also produce a feeling of euphoria very similar to that produced by other opioids.
Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:
- John Hughes and Hans Kosterlitz of Scotland isolated – from the brain of a pig – what some called "enkephalins" (from the Greek εγκέφαλος, cerebrum).
- Around the same time, in a calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what Eric Simon (who independently discovered opioid receptors in vertebral brains) later termed "endorphin" by an abbreviation of "endogenous morphine", meaning "morphine produced naturally in the body". Studies have demonstrated that human and diverse animal tissues are capable of producing morphine, which is not a peptide. They have been continually researched for their pain relieving properties and role in the feeling of pleasure.
From the words 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 'endo(genous) (mo)rphin’ (morphin being the old spelling of morphine).
The three types of endorphins that exist are made through the fragmentation of precursor proteins. The original protein is called proopiomelanocortin (POMC). This protein is fragmented into many different smaller proteins including beta-lipotropin (β-LPH). β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides giving rise to α-Endorphin, β-Endorphin, γ-Endorphin and many other peptides.
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- α-Endorphin – The smallest fragment in the family and is composed of 16 amino acids. They are the same as the first 16 amino acids as the β-endorphin. The sequenced protein has been shown to be: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH.
- β-Endorphin – The longest fragment in the family and is composed of 31 amino acids. The sequence has been shown to be: 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. .
- γ-Endorphin – The second longest fragment and is composed of 17 amino acids. It also matches the first 17 amino Acids of β-endorphin. The sequence has been shown to be: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH.
Mechanism of actionEdit
Endorphins are naturally produced in response to pain. This phenomenon happens in both the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). In the PNS, endorphins, primarily β-endorphin, are released from the pituitary gland and bind to μ-receptors. The binding of these two components inhibits the pain signal of the periphery nerves by blocking the neurotransmitter substance P. The mechanism in the CNS is similar but works by blocking a different neurotransmitter. When the endorphin binds to the μ-receptor, it inhibits the release of the neurotransmitter gamma-aminobutyric acid (GABA) which, in turn, increases the production and release of dopamine, the neurotransmitter associated with pleasure.
Their production can also be triggered by various human activities. Vigorous aerobic exercise can stimulate the release of β-endorphin which contributes to a phenomenon known as a "runner's high."
Laughter may also stimulate endorphin production; a 2011 study showed that attendees at a comedy club showed increased resistance to pain. Endorphins are also released during various activities including eating food, sex, orgasm, listening to music and eating chocolate. Research has also demonstrated meditation by trained individuals to trigger endorphin release. 
Endorphins play a major role in the body's response to inhibiting pain but endorphins have also been looked at for their role in pleasure. There has been a lot of research in the euphoric state that is produced after the release of endorphins in cases such as runner's high, orgasms, and eating appetizing food. Endorphins have also been looked into as a way to aid in the treatment of anxiety and depression through exercising.
On the other hand, endorphins may also be involved in exercise addiction. The release of endorphins a person gets while exercising will produce a feeling of euphoria. With consistent exercise, the brain may down-regulate the production of endorphins in periods of rest and a person will need to continue to exercise more intensely in order to receive the same feeling.
- 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
- "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 .
- 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.
- 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.
- "Is there a link between exercise and happiness?". 22 June 2009. Archived from the original on 14 August 2014. Retrieved 18 September 2014.
- "Role of endorphins discovered". PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1 January 1998. Retrieved 15 October 2008.
- 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.
- 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.
- 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.
- 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.
- Ambinder RF, Schuster MM (November 1979). "Endorphins: new gut peptides with a familiar face". Gastroenterology. 77 (5): 1132–40. PMID 226450.
- 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. doi:10.1073/pnas.75.10.4719. PMC 336191. PMID 216997.
- 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.
- 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. doi:10.1073/pnas.73.11.3942. PMC 431275. PMID 1069261.
- Chaudhry SR, Bhimji SS (2018). Biochemistry, Endorphin. StatPearls. StatPearls Publishing. PMID 29262177. Retrieved 20 February 2019.
- 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.
- Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (November 2008). "The runner's high: opioidergic mechanisms in the human brain" (PDF). Cerebral Cortex. 18 (11): 2523–31. doi:10.1093/cercor/bhn013. PMID 18296435.[permanent dead link]
- Kolata G (27 March 2008). "Yes, Running Can Make You High". The New York Times. ISSN 0362-4331. Retrieved 26 May 2016.
- 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.
- 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.
- 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.
- 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.