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{{short description|Peptide hormone in humans}} |
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{{protein |
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{{cs1 config|name-list-style=vanc}} |
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| Name = beta-endorphin |
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{{lowercase title}} |
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| caption = |
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{{Use dmy dates|date=June 2018}} |
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| image = beta-endorphin.png |
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| width = 300 |
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| HGNCid = 9201 |
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| Symbol = POMC |
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| AltSymbols = |
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| EntrezGene = 5443 |
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| OMIM = 176830 |
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| RefSeq = NM_000939 |
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| UniProt = P01189 |
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| PDB = |
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| ECnumber = |
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| Chromosome = 2 |
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| Arm = p |
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| Band = 23 |
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| LocusSupplementaryData = |
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}} |
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{{chembox |
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{{chembox |
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| Name = β-Endorphin |
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| verifiedrevid = 409720122 |
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| verifiedrevid = 444653150 |
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|ImageFile= |
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| ImageFile= beta-endorphin.png |
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|ImageSize= |
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| ImageSize= 250px |
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|IUPACName= |
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| ImageFile2= Beta endorphin 3D stick.png |
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|OtherNames= |
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| ImageSize2= 250px |
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| IUPACName = L-Tyrosylglycylglycyl-L-phenylalanyl-L-methionyl-L-threonyl-L-seryl-L-glutaminyl-L-lysyl-L-seryl-L-glutaminyl-L-threonyl-L-prolyl-L-leucyl-L-valyl-L-threonyl-L-leucyl-L-phenylalanyl-L-lysyl-L-asparaginyl-L-alanyl-L-isoleucyl-L-isoleucyl-L-lysyl-L-asparaginyl-L-alanyl-L-tyrosyl-L-lysyl-L-lysylglycyl-L-glutamine |
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| OtherNames= |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| IUPHAR_ligand = 1643 |
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| CASNo= |
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| CASNo_Ref = {{cascite|correct|??}} |
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| PubChem=16132316 |
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| CASNo = 60617-12-1 |
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| SMILES=CCC(C)C(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NC(C)C(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)O)NC(=O)C(C)NC(=O)C(CC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(C(C)O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C3CCCN3C(=O)C(C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CO)NC(=O)C(CCCCN)NC(=O)C(CCC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CCSC)NC(=O)C(CC4=CC=CC=C4)NC(=O)CNC(=O)CNC(=O)C(CC5=CC=C(C=C5)O)N |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 3S51P4W3XQ |
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| PubChem=16132316 |
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| ChEBI = 10415 |
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| ChemSpiderID = 28184601 |
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| SMILES = CC(C)(C(=O)N((C)CC)C(=O)N(CCCCN)C(=O)N(CC(=O)N)C(=O)N(C)C(=O)N(Cc1ccc(cc1)O)C(=O)N(CCCCN)C(=O)N(CCCCN)C(=O)NCC(=O)N(CCC(=O)N)C(=O)O)NC(=O)(C)NC(=O)(CC(=O)N)NC(=O)(CCCCN)NC(=O)(Cc2ccccc2)NC(=O)(CC(C)C)NC(=O)((C)O)NC(=O)(C(C)C)NC(=O)(CC(C)C)NC(=O)3CCCN3C(=O)((C)O)NC(=O)(CCC(=O)N)NC(=O)(CO)NC(=O)(CCCCN)NC(=O)(CCC(=O)N)NC(=O)(CO)NC(=O)((C)O)NC(=O)(CCSC)NC(=O)(Cc4ccccc4)NC(=O)CNC(=O)CNC(=O)(Cc5ccc(cc5)O)N |
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| InChI = 1/C158H253N41O44S/c1-17-84(9)126(153(237)184-102(44-29-34-65-163)137(221)188-112(74-120(168)210)142(226)173-86(11)131(215)185-110(73-94-48-52-96(206)53-49-94)146(230)179-99(41-26-31-62-160)135(219)177-98(40-25-30-61-159)134(218)172-78-124(214)175-106(158(242)243)56-59-119(167)209)195-154(238)127(85(10)18-2)194-132(216)87(12)174-143(227)113(75-121(169)211)187-136(220)100(42-27-32-63-161)180-147(231)111(72-92-38-23-20-24-39-92)186-144(228)107(68-81(3)4)190-155(239)129(89(14)203)197-152(236)125(83(7)8)193-148(232)108(69-82(5)6)189-151(235)116-45-35-66-199(116)157(241)130(90(15)204)198-140(224)104(55-58-118(166)208)182-149(233)114(79-200)191-138(222)101(43-28-33-64-162)178-139(223)103(54-57-117(165)207)181-150(234)115(80-201)192-156(240)128(88(13)202)196-141(225)105(60-67-244-16)183-145(229)109(71-91-36-21-19-22-37-91)176-123(213)77-170-122(212)76-171-133(217)97(164)70-93-46-50-95(205)51-47-93/h19-24,36-39,46-53,81-90,97-116,125-130,200-206H,17-18,25-35,40-45,54-80,159-164H2,1-16H3,(H2,165,207)(H2,166,208)(H2,167,209)(H2,168,210)(H2,169,211)(H,170,212)(H,171,217)(H,172,218)(H,173,226)(H,174,227)(H,175,214)(H,176,213)(H,177,219)(H,178,223)(H,179,230)(H,180,231)(H,181,234)(H,182,233)(H,183,229)(H,184,237)(H,185,215)(H,186,228)(H,187,220)(H,188,221)(H,189,235)(H,190,239)(H,191,222)(H,192,240)(H,193,232)(H,194,216)(H,195,238)(H,196,225)(H,197,236)(H,198,224)(H,242,243)/t84-,85-,86-,87-,88+,89+,90+,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,125-,126-,127-,128-,129-,130-/m0/s1 |
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| InChIKey = WOPZMFQRCBYPJU-NTXHZHDSBY |
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| StdInChI = 1S/C158H253N41O44S/c1-17-84(9)126(153(237)184-102(44-29-34-65-163)137(221)188-112(74-120(168)210)142(226)173-86(11)131(215)185-110(73-94-48-52-96(206)53-49-94)146(230)179-99(41-26-31-62-160)135(219)177-98(40-25-30-61-159)134(218)172-78-124(214)175-106(158(242)243)56-59-119(167)209)195-154(238)127(85(10)18-2)194-132(216)87(12)174-143(227)113(75-121(169)211)187-136(220)100(42-27-32-63-161)180-147(231)111(72-92-38-23-20-24-39-92)186-144(228)107(68-81(3)4)190-155(239)129(89(14)203)197-152(236)125(83(7)8)193-148(232)108(69-82(5)6)189-151(235)116-45-35-66-199(116)157(241)130(90(15)204)198-140(224)104(55-58-118(166)208)182-149(233)114(79-200)191-138(222)101(43-28-33-64-162)178-139(223)103(54-57-117(165)207)181-150(234)115(80-201)192-156(240)128(88(13)202)196-141(225)105(60-67-244-16)183-145(229)109(71-91-36-21-19-22-37-91)176-123(213)77-170-122(212)76-171-133(217)97(164)70-93-46-50-95(205)51-47-93/h19-24,36-39,46-53,81-90,97-116,125-130,200-206H,17-18,25-35,40-45,54-80,159-164H2,1-16H3,(H2,165,207)(H2,166,208)(H2,167,209)(H2,168,210)(H2,169,211)(H,170,212)(H,171,217)(H,172,218)(H,173,226)(H,174,227)(H,175,214)(H,176,213)(H,177,219)(H,178,223)(H,179,230)(H,180,231)(H,181,234)(H,182,233)(H,183,229)(H,184,237)(H,185,215)(H,186,228)(H,187,220)(H,188,221)(H,189,235)(H,190,239)(H,191,222)(H,192,240)(H,193,232)(H,194,216)(H,195,238)(H,196,225)(H,197,236)(H,198,224)(H,242,243)/t84-,85-,86-,87-,88+,89+,90+,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,125-,126-,127-,128-,129-,130-/m0/s1 |
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| StdInChIKey = WOPZMFQRCBYPJU-NTXHZHDSSA-N |
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}} |
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}} |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula=C<sub>158</sub>H<sub>251</sub>N<sub>39</sub>O<sub>46</sub>S |
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| C=158 | H=251 | N=39 | O=46 | S=1 |
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| Appearance= |
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| MolarMass=3464.98224 |
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| Appearance= |
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| Density= |
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| Density= |
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| MeltingPt= |
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| Solubility= |
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| Solubility= |
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}} |
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}} |
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|Section3={{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards= |
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| MainHazards= |
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| FlashPt= |
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| FlashPt= |
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| AutoignitionPt = |
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| Autoignition= |
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}} |
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'''β-]''' is an ] ] ] ] found in the ]s of both the ] and ]. |
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'''β-Endorphin''' (''beta''-endorphin) is an ] ] ] and ] that is produced in certain ]s within the ] and ].<ref name="NHM-Beta-endorphin">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | veditors = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 184, 190, 192 | edition = 2nd | chapter = Chapter 7: Neuropeptides | quote= Opioid Peptides<br />β-Endorphin (also a pituitary hormone) ...<br />Opioid peptides are encoded by three distinct genes. These precursors include POMC, from which the opioid peptide β-endorphin and several nonopioid peptides are derived, as discussed earlier; proenkephalin, from which met-enkephalin and leu-enkephalin are derived; and prodynorphin, which is the precursor of dynorphin and related peptides. Although they come from different precursors, opioid peptides share significant amino acid sequence identity. Specifically, all of the well-validated endogenous opioids contain the same four N-terminal amino acids (Tyr-Gly-Gly-Phe), followed by either Met or Leu ... Among endogenous opioid peptides, β-endorphin binds preferentially to μ receptors. ... Shared opioid peptide sequences. Although they vary in length from as few as five amino acids (enkephalins) to as many as 31 (β-endorphin), the endogenous opioid peptides shown here contain a shared N-terminal sequence followed by either Met or Leu.}}</ref> It is one of three ] that are produced in humans, the others of which include ] and ].<ref name="Endogenous opioid families - 2012 review">{{cite journal | vauthors = Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R | title = Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins | journal = ] | volume = 4 | issue = 2 | date = February 2012 | pmid = 22300099 | pmc = 3306179 | doi = 10.4155/fmc.11.195 |at= }}</ref> |
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The amino acid sequence is: ]-]-Gly-]-]-]-]-]-]-Ser-]-Thr-]-]-]-Thr-Leu-Phe-Lys-]-]-]-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu<ref></ref> |
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There are multiple forms of β-endorphins with the full sequence of ]-]-Gly-]-]-]-]-]-]-Ser-]-Thr-]-]-]-Thr-Leu-Phe-Lys-]-]-]-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu (31 amino acids) denoted as β-endorphin(1-31) and variants truncated to the first 26 and 27 amino acids as β-endorphin(1-26) and β-endorphin(1-27). <ref name="NHM-Beta-endorphin" /><ref>{{cite journal | vauthors = Pilozzi A, Carro C, Huang X | title = Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism | journal = International Journal of Molecular Sciences | volume = 22 | issue = 1 | pages = 338 | date = December 2020 | pmid = 33396962 | pmc = 7796446 | doi = 10.3390/ijms22010338 |doi-access=free }}</ref><ref></ref> However, β-endorphin(1-31) is the only form that possess a potent analgesic effect and it is the primary form located in the anterior pituitary gland, and regions such as the hypothalamus, midbrain, and amygdala.<ref name="Pilozzi2020">{{cite journal |last1=Pilozzi |first1=Alexander |last2=Carro |first2=Caitlyn |last3=Huang |first3=Xudong |title=Roles of β-endorphin in stress, behavior, neuroinflammation, and brain energy metabolism |journal=International Journal of Molecular Sciences |date=December 30, 2020 |volume=22 |issue=1 |page=338 |doi=10.3390/ijms22010338 |doi-access=free |pmid=33396962 |pmc=7796446 }}</ref> The first 16 amino acids are identical to α-endorphin. β-Endorphin is considered to be a part of the ] and ] classes of neuropeptides;<ref name="NHM-Beta-endorphin" /> all of the established endogenous opioid peptides contain the same N-terminal amino acid sequence, Tyr-Gly-Gly-Phe, followed by either {{nowrap|-Met}} or {{nowrap|-Leu}}.<ref name="NHM-Beta-endorphin" /> |
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==Formation== |
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β-endorphin is a peptide, 31 amino acids long, resulting from processing of the precursor ] (POMC). (Note, POMC also gives rise to other peptide hormones, including ACTH ( ] ), as well α- and γ-MSH ( ] ), resulting from intracellular processing by internal enzymes known as ]s.) |
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Function of β-endorphin has been known to be associated with ], thrill, ], maternal care, sexual behavior, and ]. In the broadest sense, β-endorphin is primarily utilized in the body to reduce stress and maintain homeostasis. In behavioral research, studies have shown that β-endorphin is released via ] into the ] in response to a variety of stimuli, and ] in particular.<ref name=":1">{{cite journal | vauthors = Veening JG, Barendregt HP | title = The effects of beta-endorphin: state change modification | journal = Fluids and Barriers of the CNS | volume = 12 | pages = 3 | date = January 2015 | pmid = 25879522 | pmc = 4429837 | doi = 10.1186/2045-8118-12-3 |doi-access=free }}</ref> |
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β-endorphin is found in neurons of the ], as well as the ] gland. |
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==Formation and structure== |
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==Function== |
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β-Endorphin is found in neurons of the ], as well as the ] gland. It is derived from ], which is produced in the ] from a larger peptide precursor, ] (POMC).<ref name=":2" /> POMC is cleaved into two neuropeptides, ] (ACTH) and β-lipotropin.<ref name=":0">{{cite journal | vauthors = Dalayeun JF, Norès JM, Bergal S | title = Physiology of beta-endorphins. A close-up view and a review of the literature | journal = Biomedicine & Pharmacotherapy | volume = 47 | issue = 8 | pages = 311–20 | pmid = 7520295 | doi = 10.1016/0753-3322(93)90080-5 | year = 1993 }}</ref> The formation of β-endorphin is then the result of cleavage of the C-terminal region of β-lipotropin, producing a 31 amino acid-long neuropeptide with an alpha-helical secondary structure. However, POMC also gives rise to other peptide hormones, including α- and γ-] (MSH), resulting from intracellular processing by internal enzymes known as ]s. |
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A significant factor that differentiates β-endorphin from other endogenous opioids is its ] for and lasting effect on ].<ref name=":2" /> The structure of β-endorphin in part accounts for this through its resistance to ]s, as its secondary structure makes it less vulnerable to degradation.<ref name=":2" /> |
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It is an agonist of the opioid receptors, with evidence suggesting it serves as the endogenous ] of the ], the same receptor to which the chemicals extracted from ], such as ], have their ] and ] effects (indeed, the μ-opioid receptor was named based on its most renowned ligand, morphine). |
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] gene in the pituitary gland. Portions of the second and third exon of this gene make up the proopiomelanocortin protein. The cleavage of the C-terminal end of this protein produces β-lipotropin, which is then cleaved again to form β-endorphin. The proopiomelanocortin protein is also a precursor to other neuropeptides and hormones, such as adrenocorticotropic hormone.]] |
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] with each amino acid labeled.]] |
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{{clear}} |
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==Function and effects== |
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==History== |
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β-Endorphin function is said to be divided into two main categories: local function and global function. Global function of β-endorphin is related to decreasing bodily stress and maintaining homeostasis resulting in pain management, reward effects, and behavioral stability. β-Endorphin in global pathways diffuse to different parts of the body through cerebral spinal fluid in the spinal cord, allowing for β-endorphin release to affect the peripheral nervous system. Localized function of β-endorphin results in release of β-endorphin in different brain regions such as the amygdala or the hypothalamus.<ref name=":1" /> The two main methods by which β-endorphin is utilized in the body are peripheral hormonal action<ref name=":6" /> and neuroregulation. It is considered to act both as a ] and a ] since it produces effects on distant targets that have increased stability and longevity when compared to other neurotransmitters.<ref name="Pilozzi2020"></ref> β-endorphin and other ]s are often released with ] to modulate hormone system functioning. Neuroregulation by β-endorphin occurs through interference with the function of another neuropeptide, either by direct inhibition of neuropeptide release or induction of a signaling cascade that reduces a neuropeptide's effects.<ref name=":0" /> |
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β-endorphin was discovered from camel pituitary extracts by C.H. Li and David Chung.<ref>{{cite journal | doi = 10.1073/pnas.73.4.1145 | url = http://www.pnas.org/cgi/content/abstract/73/4/1145 | author = Choh Hao Li and David Chung | title = Isolation and Structure of an Untriakontapeptide with Opiate Activity from Camel Pituitary Glands | journal = PNAS | year = 1976 | volume = 73 | issue = 4 | pages = 1145–1148 | pmid = 1063395 | pmc = 430217}}</ref> The discovery was amidst a flurry of discoveries made in the opioid field of "endogenous opiates", including ], ], and ]. Shortly thereafter, also in C.H. Li's laboratory, the opioid effects of this peptide were characterized.<ref>{{Cite journal | doi = 10.1073/pnas.73.8.2895 | url = http://www.pnas.org/cgi/content/abstract/73/4/1145 | author = Horace H. Loh, L. F. Tseng, Eddie Wei, and Choh Hao Li | title = β-Endorphin is a Potent Analgesic Agent | journal = PNAS | year = 1976 | volume = 73 | issue = 8 | pages = 2895–2898 | pmid = 8780 | pmc = 430793}}</ref> Some notable early questions which were investigated included anatomical questions (where in the body? where in the brain? where in the neuron?), pharmacological questions (how similar to morphine? how does potency differ? what part of the molecule confers opioid activity?), biochemical questions (how is it biosynthesized? how is the activity regulated? how is it metabolized?), behavioral questions (what is the effect of endogenous β-endorphin on activity levels), clinical questions (do deficiencies in endogenous β-endorphin lead to psychological disorders?), and therapeutic questions (is β-endorphin a viable treatment for morphine and heroin addiction, as well as chronic pain disorders?). |
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== Effects == |
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=== Opioid agonist === |
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β-Endorphin is an agonist of the ]s; it preferentially binds to the ].<ref name="NHM-Beta-endorphin" /> Evidence suggests that it serves as a primary endogenous ] for the ],<ref name="NHM-Beta-endorphin" /><ref name="IUPHAR μ-opioid receptor">{{cite web|date=15 March 2017|title=Opioid receptors: μ receptor|url=http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=319|access-date=26 May 2017|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|quote=Principal endogenous agonists (Human)<br />β-endorphin (POMC, P01189), enkephalin (PENK, P01210), enkephalin (PENK, P01210) ...<br />Comments: β-Endorphin is the highest potency endogenous ligand|vauthors=Borsodi A, Caló G, Chavkin C, Christie MJ, Civelli O, Cox BM, Devi LA, Evans C, Henderson G, Höllt V, Kieffer B, Kitchen I, Kreek MJ, Liu-Chen LY, Meunier JC, Portoghese PS, Shippenberg TS, Simon EJ, Toll L, Traynor JR, Ueda H, Wong YH}}</ref> the same receptor to which the chemicals extracted from ], such as ], derive their ] properties. β-Endorphin has the highest binding affinity of any endogenous opioid for the μ-opioid receptor.<ref name="NHM-Beta-endorphin" /><ref name=":2" /><ref name="IUPHAR μ-opioid receptor" /> Opioid receptors are a class of ], such that when β-endorphin or another opioid binds, a signaling cascade is induced in the cell.<ref>{{cite journal|vauthors=Livingston KE, Traynor JR|year=2018|title=Allostery at opioid receptors: modulation with small molecule ligands|journal=British Journal of Pharmacology|volume=175|issue=14|pages=2846–2856|doi=10.1111/bph.13823|pmc=6016636|pmid=28419415}}</ref> Acetylation of the N-terminus of β-endorphin, however, inactivates the neuropeptide, preventing it from binding to its receptor.<ref name=":2" /> The opioid receptors are distributed throughout the central nervous system and within the peripheral tissue of neural and non-neural origin. They are also located in high concentrations in the ], ], and the ].<ref>{{cite journal|vauthors=Al-Hasani R, Bruchas MR|date=December 2011|title=Molecular mechanisms of opioid receptor-dependent signaling and behavior|journal=Anesthesiology|volume=115|issue=6|pages=1363–81|doi=10.1097/ALN.0b013e318238bba6|pmc=3698859|pmid=22020140}}</ref> |
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]s (VDCCs) are important membrane proteins that mediate the depolarization of neurons, and play a major role in promoting the release of neurotransmitters. When endorphin molecules bind to opioid receptors, G proteins activate and dissociate into their constituent Gα and Gβγ sub-units. The Gβγ sub-unit binds to the intracellular loop between the two trans-membrane helices of the VDCC. When the sub-unit binds to the voltage-dependent calcium channel, it produces a voltage-dependent block, which inhibits the channel, preventing the flow of calcium ions into the neuron. Embedded in the cell membrane is also the ]. When a Gβγ or Gα(GTP) molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are pumped out of the neuron.<ref>{{cite journal|vauthors=Yamada M, Inanobe A, Kurachi Y|date=December 1998|title=G protein regulation of potassium ion channels|url=http://pharmrev.aspetjournals.org/content/50/4/723|journal=Pharmacological Reviews|volume=50|issue=4|pages=723–60|pmid=9860808}}</ref><ref>{{cite journal|vauthors=Reuveny E, Slesinger PA, Inglese J, Morales JM, Iñiguez-Liuhi JA, Lefkowitz RJ, Bourne HR, Jan YN, Jan LY|date=July 1994|title=Activation of the Cloned Muscarinic Potassium Channel by G Protein βγ Subunits|journal=Nature|volume=370|issue=6485|pages=143–146|doi=10.1038/370143a0|pmid=8022483|bibcode=1994Natur.370..143R|s2cid=4345632}}</ref> The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane ]. This is when there is a change in the membrane's potential, so that it becomes more negative. The reduction in calcium ions causes a reduction of neurotransmitter release because calcium is essential for this event to occur.<ref>{{cite journal|vauthors=Kosten TR, George TP|date=July 2002|title=The neurobiology of opioid dependence: implications for treatment|journal=Science & Practice Perspectives|volume=1|issue=1|pages=13–20|doi=10.1151/spp021113|doi-broken-date=10 November 2024 |pmc=2851054|pmid=18567959}}</ref> This means that neurotransmitters such as ] and ] cannot be released from the presynaptic terminal of the neurons. Substance P is a believed to help sensitize postsynaptic neurons to glutamate, aiding in the transmission of pain signals from periphery nerves to the brain.<ref>{{cite journal |last1=Chaudrhy |first1=Shazia |last2=Gossman |first2=William |title=Biochemistry, Endorphins |url=https://www.ncbi.nlm.nih.gov/books/NBK470306/ |website=National Institute of Health |date=2024 |publisher=StatPearls |pmid=29262177 |access-date=10 November 2024}}</ref> These neurotransmitters are vital in the transmission of pain, and as β-Endorphin reduces the release of these substances, there is a strong analgesic effect. |
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It is used as an analgesic in the body to numb or dull pains. That is the reason why humans start to feel better immediately after an acute physical trauma even though the symptoms are still present. The reason the pain dulls is because it binds to and activates opioid receptors. β-endorphin has approximately 80 times the analgesic potency of ]. |
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=== Pain management === |
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β-endorphin is believed to have a number of other benefits, including: |
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β-Endorphin has been primarily studied for its influence on ] (i.e., ] perception). β-endorphin modulates pain perception both in the ] and the ]. When pain is perceived, pain receptors (]s) send signals to the dorsal horn of the ] and then up to the ] through the release of a ] called ].<ref name=":0" /><ref name=":1" /><ref name=":4">{{cite journal | vauthors = Sprouse-Blum AS, Smith G, Sugai D, Parsa FD | title = Understanding endorphins and their importance in pain management | journal = Hawaii Medical Journal | volume = 69 | issue = 3 | pages = 70–1 | date = March 2010 | pmid = 20397507 | pmc = 3104618 }}</ref><ref name=":5">{{cite journal | vauthors = Luan YH, Wang D, Yu Q, Chai XQ | title = Action of β-endorphin and nonsteroidal anti-inflammatory drugs, and the possible effects of nonsteroidal anti-inflammatory drugs on β-endorphin | language = en | journal = Journal of Clinical Anesthesia | volume = 37 | pages = 123–128 | date = February 2017 | pmid = 28235500 | doi = 10.1016/j.jclinane.2016.12.016 }}</ref> In the ], this signal causes the recruitment of ], white blood cells of the immune system, to the area where pain was perceived.<ref name=":5" /> T-lymphocytes release β-endorphin in this localized region, allowing it to bind to opioid receptors, causing direct inhibition of substance P.<ref name=":5" /><ref>{{cite journal | vauthors = Plein LM, Rittner HL | title = Opioids and the immune system – friend or foe | journal = British Journal of Pharmacology | volume = 175 | issue = 14 | pages = 2717–2725 | pmid = 28213891 | doi = 10.1111/bph.13750 | pmc = 6016673 | year = 2018 }}</ref> In the ], β-endorphin binds to opioid receptors in the dorsal root and inhibits the release of substance P in the spinal cord, reducing the number of excitatory pain signals sent to the brain.<ref name=":5" /><ref name=":4" /> The hypothalamus responds to the pain signal by releasing β-endorphin through the ] network, which mainly acts to inhibit the release of ], a ] which prevents the release of ].<ref name=":0" /><ref name=":4" /> Thus, the inhibition of GABA release by β-endorphin allows for a greater release of dopamine, in part contributing to the analgesic effect of β-endorphin.<ref name=":0" /><ref name=":4" /> The combination of these pathways reduces pain sensation, allowing for the body to stop a pain impulse once it has been sent. |
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β-Endorphin has approximately 18 to 33 times the analgesic potency of ],<ref>{{cite journal|author-link1=Horace Loh | 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 = 2895–8 | date = August 1976 | pmid = 8780 | pmc = 430793 | doi = 10.1073/pnas.73.8.2895 | bibcode = 1976PNAS...73.2895L | doi-access = free }}</ref> though its hormonal effect is species dependent.<ref name=":6">{{cite journal | vauthors = Foley KM, Kourides IA, Inturrisi CE, Kaiko RF, Zaroulis CG, Posner JB, Houde RW, Li CH | title = beta-Endorphin: analgesic and hormonal effects in humans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 76 | issue = 10 | pages = 5377–81 | date = October 1979 | pmid = 291954 | pmc = 413146 | doi = 10.1073/pnas.76.10.5377 | bibcode = 1979PNAS...76.5377F | doi-access = free }}</ref> |
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*Boosting the ]{{Fact|date=April 2007}} |
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*Slowing the growth of ] cells <ref></ref> |
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*Promoting feeling of well-being |
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*Increasing relaxation |
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==References== |
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===Exercise=== |
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{{main|Neurobiological effects of physical exercise#β-Endorphin}} |
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{{Reflist}} |
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β-Endorphin release in response to exercise has been known and studied since at least the 1980s.<ref name="pmid6091217">{{cite journal | vauthors = Harber VJ, Sutton JR | title = Endorphins and exercise | journal = Sports Medicine | volume = 1 | issue = 2 | pages = 154–71 | date = March–April 1984 | pmid = 6091217 | doi = 10.2165/00007256-198401020-00004 | s2cid = 6435497 }}</ref> Studies have demonstrated that serum concentrations of endogenous opioids, in particular β-endorphin and ], increase in response to both acute exercise and training.<ref name="pmid6091217" /> The release of β-endorphin during exercise is associated with a phenomenon colloquially known in popular culture as a '']''.<ref>{{cite web|url=http://www.webmd.com/depression/guide/exercise-depression|title=Exercise and Depression| vauthors = Goldberg J |date=19 February 2014|website=WebMD|access-date=14 July 2014}}</ref> |
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=== Sunlight === |
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There is evidence that β-endorphin is released in response to ], either through sun exposure or artificial tanning.<ref>{{Cite web |date=2014-06-19 |title=Addicted to the Sun |url=https://hms.harvard.edu/news/addicted-sun |access-date=2023-08-29 |website=hms.harvard.edu |language=en}}</ref> This is thought to contribute to ] among excessive ] and users of ] despite health risks. |
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=== Addiction === |
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Studies suggest that β-Endorphins could be correlated with ] due to their involvement with the brain's ].<ref>{{cite journal |last1=Zalewska-Kaszubska |first1=Jadwiga |last2=Czarnecka |first2=Elżbieta |title=Deficit in beta-endorphin peptide and tendency to alcohol abuse |journal=Peptides |date=April 2005 |volume=26 |issue=4 |page=702 |doi=10.1016/j.peptides.2004.11.010 |pmid=15752586 |url=https://www.sciencedirect.com/science/article/pii/S0196978104005091#:~:text=Beta%2Dendorphin%20is%20functionally%20connected,drugs%20to%20restore%20this%20equilibrium. |access-date=October 26, 2024}}</ref> Alcohol consumption causes an increase in the release of β-Endorphins within the regions of the brain's reward system. Regular and long-term consumption of alcohol consequently leads to a deficit in the levels of β-Endorphins that requires continuous consumption of alcohol to replenish. Individuals with a deficiency of β-Endorphins due to genetics may be more vulnerable to alcohol addiction as a result.<ref>{{cite journal |last1=Zalewska-Kaszubska |first1=Jadwiga |last2=Czarnecka |first2=Elżbieta |title=Deficit in beta-endorphin peptide and tendency to alcohol abuse |journal=Peptides |date=April 2005 |volume=26 |issue=4 |pages=701–705 |doi=10.1016/j.peptides.2004.11.010 |pmid=15752586 |url=https://www.sciencedirect.com/science/article/pii/S0196978104005091#:~:text=Beta%2Dendorphin%20is%20functionally%20connected,drugs%20to%20restore%20this%20equilibrium. |access-date=October 26, 2024}}</ref> |
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== Mechanism of action == |
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β-Endorphin acts as an agonist that binds to various types of ]s (GPCRs), most notably to the mu, delta, and kappa opioid receptors. Binding to these receptors prevents the release of Substance P in the case of the ], and the inhibitory neurotransmitter, GABA, in the ]<ref>{{cite journal |last1=Graefe |first1=B. Steven |last2=Rahimi |first2=Nader |last3=Shamim |first3=S. Mohiuddin |title=Biochemistry, Substance P |url=https://www.ncbi.nlm.nih.gov/books/NBK554583/ |website=National Institute of Health |date=2024 |publisher=StatPearls |pmid=32119470 |access-date=10 November 2024}}</ref> The receptors are responsible for supra-spinal analgesia.{{medical citation needed|date=January 2019}} |
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== History == |
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β-Endorphin was discovered in camel pituitary extracts by C.H. Li and David Chung.<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 = 1145–8 | date = April 1976 | pmid = 1063395 | pmc = 430217 | doi = 10.1073/pnas.73.4.1145 | bibcode = 1976PNAS...73.1145L | doi-access = free }}</ref> The primary structure of β-endorphin was unknowingly determined 10 years earlier, when Li and colleagues analyzed the sequence of another neuropeptide produced in the pituitary gland, ]. They noticed that the C-terminus region of this neuropeptide was similar to that of some ]s, suggesting that it may have a similar function to these neuropeptides. The C-terminal sequence of γ-lipotropin turned out to be the primary sequence of the β-endorphin.<ref name=":2">{{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 = T13-25 | date = May 2016 | pmid = 26903509 | doi = 10.1530/JME-16-0033 | doi-access = free }}</ref> |
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== References == |
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{{reflist|33em}} |
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== External links == |
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== External links == |
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* {{PubChem|16132316}} - β-endorphin |
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* {{PubChem|16132316}} – β-endorphin |
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* {{PubChem|3081525}} - β-endorphin (1-9) |
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* {{PubChem|3081525}} – β-endorphin (1-9) |
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* {{PubChem|133304}} - β-endorphin (2-9) |
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* {{PubChem|133304}} – β-endorphin (2-9) |
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* {{MeshName|β-endorphin}} |
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* {{MeshName|β-endorphin}} |
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{{Opioid peptides}} |
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{{Opioid peptides}} |
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{{Opioidergics}} |
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{{DEFAULTSORT:Endorphin, beta-}} |
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