Wikipedia

Endorphins

(Redirected fromEndorphin)

For other uses, seeEndorphins (disambiguation).

Endorphins(contracted fromendogenous morphine)[1][2][3]arepeptidesproduced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in thepituitary glandof the brain. Endorphins areendogenouspainkillersoften produced in the brain andadrenal medulladuringphysical exerciseororgasmand inhibit pain,muscle cramps,and relieve stress.[4][5][6][7]

Chemical structure of Met-enkephalin
Physical activity and exercise release the most endorphins
Cocoa powderhelps most among the edible substances to produce endorphins in human body

History

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Opioid peptidesin the brain were first discovered in 1973 by investigators at the University of Aberdeen,John HughesandHans Kosterlitz.They isolated "enkephalins"(from theGreekεγκέφαλος) frompigbrain,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-relievinganalgesiceffects ofmorphineand 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 ofmorphine.[11][12]

Rabi Simantov andSolomon H. Snyderisolated morphine-like peptides fromcalfbrain.[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 FeldbergandDerek George Smythin 1977 confirmed this, finding β-endorphin to be more potent than morphine. They also confirmed that its effects were reversed bynaloxone,anopioid antagonist.[19]

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced morphine,[20][21]which is not apeptide.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 wordendorphinis derived fromἔνδον/Greek:éndonmeaning "within" (endogenous,ἐνδογενής/Greek:endogenes,"proceeding from within" ), andmorphine,fromMorpheus(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 threeendogenous opioidpeptides:α-endorphin,β-endorphin,andγ-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 thepituitary gland.[29][30][31]All three types of endorphins are fragments of the precursor proteinproopiomelanocortin(POMC). At thetrans-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 intoadrenocorticotropin(ACTH) andbeta-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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Noradrenalinehas been shown to increase endorphins production within inflammatory tissues, resulting in ananalgesic effect;[36]the stimulation ofsympathetic nervesby electro-acupuncture is believed to be the cause of its analgesic effects.[citation needed]

Mechanism of action

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Endorphins are released from the pituitary gland, typically in response to pain, and can act in both thecentral nervous system(CNS) and theperipheral nervous system(PNS). In the PNS, β-endorphin is the primary endorphin released from thepituitary gland.Endorphins inhibit transmission of pain signals by binding μ-receptors of peripheral nerves, which block their release of neurotransmittersubstance 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 ofdopamine,a neurotransmitter associated with reward learning.[27][37]

Functions

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Endorphins play a major role in the body's inhibitory response to pain. Research has demonstrated thatmeditationby trained individuals can be used to trigger endorphin release.[38][failed verification]Laughtermay also stimulate endorphin production and elevate one'spain threshold.[39]

Endorphin production can be triggered by vigorousaerobic exercise.The release of β-endorphin has been postulated to contribute to the phenomenon known as "runner's high".[40][41]However, several studies have supported the hypothesis that the runner's high is due to the release ofendocannabinoidsrather than that of endorphins.[42]Endorphins may contribute to the positive effect of exercise onanxietyanddepression.[43]The same phenomenon may also play a role inexercise addiction.Regular intense exercise may cause the brain to downregulate the production of endorphins in periods of rest to maintainhomeostasis,causing a person to exercise more intensely in order to receive the same feeling.[44]

See also

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References

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