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Endorfinlar

Endorfinlar (endogen morfindan olingan)[1][2][3] – miyada ishlab chiqariladigan peptidlar boʻlib, ogʻriq sezgisini kamaytiradi va yaxshi kayfiyatni oshiradi. Ular miyaning gipofiz bezida ishlab chiqariladi va saqlanadi. Endorfinlar koʻpincha jismoniy mashqlar yoki jinsiy zoʻriqish paytida miya va buyrak usti bezida ishlab chiqariladigan endogen ogʻriq qoldiruvchi vositalar boʻlib, ogʻriqni, mushaklar tortishishini kamaytiradi va stressdan xalos qiladi[4][5][6][7].

Endorfinning kimyoviy tuzilishi
Endorfinlarni eng koʻp jismoniy faollik va jismoniy mashqlar chiqaradi.
Kakao kukuni inson tanasida endorfin ishlab chiqarishga eng koʻp yordam beradi.

Tarixi

tahrir

Miyadagi opioid peptidlar birinchi marta 1973-yilda Aberdin universiteti tadqiqotchilari John Hughes va Hans Kosterlitz tomonidan kashf etilgan. Ular choʻchqa miyasidan Met-enkefalin va Leu-enkefalin deb nomlanuvchi „enkefalinlar“ (yunoncha εγκέφαλος cerebrum) ni ajratib olishgan[8][9][10][11]. Bu morfin va boshqa opioidlarning ogʻriq qoldiruvchi taʼsirini yuzaga keltirish uchun taklif qilingan retseptorning kashf etilishidan keyin sodir boʻlgan. Kashfiyot Kosterlitz va Hughesning endogen opioid ligandlarini aniqlashga turtki boʻlgan[11]. Bu davrdagi tadqiqotlar morfinga xos boʻlgan addiktiv (giyohvandlik) xususiyatlarga ega boʻlmagan ogʻriq qoldiruvchi vositani topishga qaratilgan edi[11][12]. Rabi Simantov va Solomon X. Snyder buzoq miyasidan morfinga oʻxshash peptidlarni ajratib olgan[13]. Opioid retseptorlarini mustaqil ravishda kashf etgan Eric J. Simon keyinchalik bu peptidlarni endorfinlar deb atagan[14]. Bu atama mohiyatan morfinga oʻxshash taʼsirga ega boʻlgan har qanday peptidga tegishli edi[15]. 1976-yilda Choh Hao Li va David Chung opioid faolligi uchun tuya gipofiz bezidan ajratilgan α-, β- va γ-endorfinlarning ketma-ketligini qayd etdilar[16][17]. Li β-endorfin kuchli ogʻriq qoldiruvchi taʼsirga ega ekanligi aniqlandi[18]. 1977-yilda Wilhelm Feldberg va Derek George Smyth buni tasdiqlab, β-endorfin morfinga qaraganda kuchliroq ekanligini aniqladilar. Shuningdek, uning taʼsiri opioid antagonisti boʻlgan nalokson bilan qaytarilgani tasdiqlandi[19]. Keyingi tadqiqotlar enkefalinlar, endorfinlar va organizmda tabiiy ravishda hosil boʻladigan morfin oʻrtasidagi farqni aniqladi. Bunda morfin peptid hisoblanmasligi maʼlum boʻldi[20][21]. Opioid peptidlar ularning prekursor propeptidiga asoslanib tasniflanadi: barcha endorfinlar proopiomelanokortindan (POMK) hosil boʻladi, bu prekursor proenkefalin A tomonidan hamda predinorfin tomonidan sintezlanadi[22][23].

Etimologiyasi

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Endorfin soʻzi ἔνδον / yunoncha: éndon „ichida“ degan maʼnoni anglatadi (endogenous, ἐνδογενής / yunoncha: endogenes, „ichkaridan kelib chiqqan“) va morfin, Morpheus (yunoncha: Morpheus), yunon mifologiyasidagi tushlar xudosi maʼnosini bildiradi. Endorfin ’endo (genous) (mo) rfinʼ (morfinning eski imlosi) qisqarishidir.

Turlari

tahrir

Endorfinlar sinfi uchta opioid peptiddan iborat: α-endorfin, β-endorfinva γ-endorfin[24]. Endorfinlarning barchasi prekursor oqsilidan, proopiomelanokortindan sintezlanadi va ularning barchasi N-terminalida Met-enkefalin motivini oʻz ichiga oladi: Tyr-Gly-Gly-Phe-Met[25]. α-endorfin va γ-endorfin Thr(16)-Leu(17) qoldiqlari va Leu(17)-Phe(18) oʻrtasida β-endorfinning proteolitik boʻlinishi natijasida hosil boʻladi[26]. α-endorfin eng qisqa, β-endorfin esa eng uzun koʻrsatkichga ega. α-endorfin va γ-endorfin asosan oldingi va oraliq gipofiz bezida joylashgan[27]. β-endorfin oʻzining opioid faolligi boʻyicha oʻrganilgan boʻlsa-da, α-endorfin va γ-endorfin opiat retseptorlariga moyil emas, shuning uchun tanaga β-endorfin kabi taʼsir qilmaydi. Baʼzi tadqiqotlarda α-endorfin faolligi psixostimulyatorlarga va γ-endorfin faolligi nevroleptiklarga oʻxshash deb tavsiflangan[27].

Ism Ketma-ketlik Malumot
α-endorfin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH [28][29]
β-endorfin 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 [30][31]
γ-endorfin Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH [28][29]

Sintezlanishi

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Endorfin prekursorlari asosan gipofiz bezida ishlab chiqariladi[32][33][34]. Endorfinlarning har uchala turi ham proopiomelankortin (POMC) prekursor oqsilining fragmentlaridir. Trans-Golji tarmogʻida POMC membrana bilan bogʻlangan oqsil, karboksipeptidaza E (CPE) bilan bogʻlanadi[35][36]. Sutemizuvchilarda pro-peptid konvertaz 1 (PC1) POMC ni adrenokortikotropin (ACTH) va beta-lipotropin (β-LPH) ga ajratadi[35]. Opiat faolligi kam boʻlgan β-LFG gipofiz gormoni keyinchalik doimiy ravishda turli peptidlarga, jumladan, α-endorfin, β-endorfin va γ-endorfinlarga parchalanadi[37][38][39]. α-endorfin va γ-endorfinning shakllanishi β-endorfinning proteolitik parchalanishidan kelib chiqadi[40].

Tartibga solish

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Noradrenalin yalligʻlanish toʻqimalarda endorfinlar ishlab chiqarilishini oshiradi, buning natijasida ogʻriq qoldiruvchi taʼsir paydo boʻladi[41]. Simpatik nerv sistemasining elektro-akupunktura bilan stimulyatsiyasi uning ogʻriq qoldiruvchi taʼsiriga sabab boʻlishi mumkin[42].

Harakat mexanizmi

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Endorfinlar odatda ogʻriqlarga javoban gipofiz bezidan chiqariladi va markaziy asab tizimida (CNS) va periferik asab tizimida (PNS) taʼsir qilishi mumkin. PNSda β-endorfin gipofiz bezidan ajralib chiqadigan asosiy endorfindir. Endorfinlar periferik nervlarning μ-retseptorlariga bogʻlanish orqali ogʻriq signallarining uzatilishini toʻxtatadi, bu esa ularning P moddasi deb ataluvchi neyrotransmitterni ajralib chiqishini oldini oladi. Markaziy asab tizimidagi mexanizm ham oʻxshash, ammo u boshqa neyrotransmitter – gamma-aminomoy kislotasi (GABA) ni toʻxtatish orqali hosil boʻladi. Oʻz navbatida, GABA ingibirlanishi dofamin ishlab chiqarilishi va ajralib chiqishini oshiradi[43][44].

Manbalar

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  1. ↑ "Endogenous morphine: up-to-date review 2011". Folia Biologica 58 (2): 49–56. 1515. PMID 22578954. http://fb.cuni.cz/file/5635/FB2012A0008.pdf. "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 (2017-yil 15-mart). — „Comments: β-Endorphin is the highest potency endogenous ligand ... Morphine occurs endogenously.“. Qaraldi: 2024-yil 1-noyabr.
  3. ↑ "Endogenous formation of morphine in human cells". Proceedings of the National Academy of Sciences of the United States of America 101 (39): 14091–14096. September 2004. doi:10.1073/pnas.0405430101. PMID 15383669. PMC 521124. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=521124. 
  4. ↑ "Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism". International Journal of Molecular Sciences 22 (1): 338. December 2020. doi:10.3390/ijms22010338. PMID 33396962. PMC 7796446. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7796446. 
  5. ↑ "Release of beta endorphin and met-enkephalin during exercise in normal women: response to training". British Medical Journal 288 (6435): 1950–1952. June 1984. doi:10.1136/bmj.288.6435.1950. PMID 6329401. PMC 1442192. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1442192. 
  6. ↑ „Endorphins: What They Are and How to Boost Them“ (en). Cleveland Clinic. Qaraldi: 2024-yil 1-noyabr.
  7. ↑ "Beta-endorphin response to exercise. An update". Sports Medicine 24 (1): 8–16. July 1997. doi:10.2165/00007256-199724010-00002. PMID 9257407. 
  8. ↑ „Role of endorphins discovered“. PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System (1998-yil 1-yanvar). Qaraldi: 2008-yil 15-oktyabr.
  9. ↑ "Identification of two related pentapeptides from the brain with potent opiate agonist activity". Nature 258 (5536): 577–580. December 1975. doi:10.1038/258577a0. PMID 1207728. https://archive.org/details/sim_nature-uk_1975-12-18_258_5536/page/n23. 
  10. ↑ „Endogenous Opioids“, The Opiate Receptors, The Receptors (en). Totowa, NJ: Humana Press, 2011 — 93–120-bet. DOI:10.1007/978-1-60761-993-2_5. ISBN 978-1-60761-993-2. 
  11. ↑ 11,0 11,1 11,2 "75 years of opioid research: the exciting but vain quest for the Holy Grail". British Journal of Pharmacology 147 (Suppl 1): S153–S162. January 2006. doi:10.1038/sj.bjp.0706435. PMID 16402099. PMC 1760732. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1760732. 
  12. ↑ Neuroscience, 6th, New York: Sunderland, 2018. ISBN 9781605353807. OCLC 990257568. 
  13. ↑ "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. July 1976. doi:10.1073/pnas.73.7.2515. PMID 1065904. PMC 430630. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=430630. 
  14. ↑ "Effect of the opiate antagonist naloxone on body temperature in rats". Life Sciences 17 (6): 927–931. September 1975. doi:10.1016/0024-3205(75)90445-2. PMID 1195988. 
  15. ↑ „POMC-Derived Opioid Peptides“, Handbook of Biologically Active Peptides (en). Elsevier, 2013 — 1592–1595-bet. DOI:10.1016/b978-0-12-385095-9.00217-7. ISBN 978-0-12-385095-9. 
  16. ↑ "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. April 1976. doi:10.1073/pnas.73.4.1145. PMID 1063395. PMC 430217. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=430217. 
  17. ↑ "60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective". Journal of Molecular Endocrinology 56 (4): T13–T25. May 2016. doi:10.1530/JME-16-0033. PMID 26903509. 
  18. ↑ "beta-endorphin is a potent analgesic agent". Proceedings of the National Academy of Sciences of the United States of America 73 (8): 2895–2898. August 1976. doi:10.1073/pnas.73.8.2895. PMID 8780. PMC 430793. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=430793. 
  19. ↑ "C-fragment of lipotropin--an endogenous potent analgesic peptide". British Journal of Pharmacology 60 (3): 445–453. July 1977. doi:10.1111/j.1476-5381.1977.tb07521.x. PMID 560894. PMC 1667279. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1667279. 
  20. ↑ "Endogenous formation of morphine in human cells". Proceedings of the National Academy of Sciences of the United States of America 101 (39): 14091–14096. September 2004. doi:10.1073/pnas.0405430101. PMID 15383669. PMC 521124. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=521124. 
  21. ↑ "De novo biosynthesis of morphine in animal cells: an evidence-based model". Medical Science Monitor 12 (10): RA207–RA219. October 2006. PMID 17006413. 
  22. ↑ Neuroscience, 6th, New York: Sunderland, 2018. ISBN 9781605353807. OCLC 990257568. 
  23. ↑ "Opioid Receptors". Annual Review of Medicine 67 (1): 433–451. 2016-01-14. doi:10.1146/annurev-med-062613-093100. PMID 26332001. 
  24. ↑ "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins". Future Medicinal Chemistry 4 (2): 205–226. February 2012. doi:10.4155/fmc.11.195. PMID 22300099. PMC 3306179. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3306179. 
  25. ↑ Neuroscience, 6th, New York: Sunderland, 2018. ISBN 9781605353807. OCLC 990257568. 
  26. ↑ "Action of proteolytic enzymes on lipotropins and endorphins: biosynthesis, biotransformation and fate". Pharmacology & Therapeutics 24 (3): 321–354. January 1984. doi:10.1016/0163-7258(84)90008-1. PMID 6087385. 
  27. ↑ 27,0 27,1 Endorphins and schizophrenia, Progress in Brain Research, 1992 — 433–53-bet. 
  28. ↑ 28,0 28,1 "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. November 1976. doi:10.1073/pnas.73.11.3942. PMID 1069261. PMC 431275. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=431275. 
  29. ↑ 29,0 29,1 Neuroscience, 6th, New York: Sunderland, 2018. ISBN 9781605353807. OCLC 990257568. 
  30. ↑ „Biochemistry, Endorphin“, StatPearls. StatPearls Publishing, 2018. Qaraldi: 2019-yil 20-fevral. 
  31. ↑ "Endorphins: new gut peptides with a familiar face". Gastroenterology 77 (5): 1132–1140. November 1979. doi:10.1016/S0016-5085(79)80089-X. PMID 226450. https://archive.org/details/sim_gastroenterology_1979-11_77_5/page/n229. 
  32. ↑ "Action of proteolytic enzymes on lipotropins and endorphins: biosynthesis, biotransformation and fate". Pharmacology & Therapeutics 24 (3): 321–354. January 1984. doi:10.1016/0163-7258(84)90008-1. PMID 6087385. 
  33. ↑ "Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain". Endocrinology 145 (3): 1331–1341. March 2004. doi:10.1210/en.2003-1287. PMID 14630714. 
  34. ↑ "Posttranslational modifications of proopiomelanocortin in vertebrates and their biological significance". Frontiers in Endocrinology 4: 143. October 2013. doi:10.3389/fendo.2013.00143. PMID 24146662. PMC 3797980. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3797980. 
  35. ↑ 35,0 35,1 "Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain". Endocrinology 145 (3): 1331–1341. March 2004. doi:10.1210/en.2003-1287. PMID 14630714. 
  36. ↑ "Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells". Journal of Molecular Neuroscience 22 (1–2): 63–71. 2004. doi:10.1385/jmn:22:1-2:63. PMID 14742911. 
  37. ↑ "Endorphins: new gut peptides with a familiar face". Gastroenterology 77 (5): 1132–1140. November 1979. doi:10.1016/S0016-5085(79)80089-X. PMID 226450. 
  38. ↑ "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. October 1978. doi:10.1073/pnas.75.10.4719. PMID 216997. PMC 336191. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=336191. 
  39. ↑ "Opioid peptides endorphins in pituitary and brain". Science 193 (4258): 1081–1086. September 1976. doi:10.1126/science.959823. PMID 959823. https://archive.org/details/sim_science_1976-09-17_193_4258/page/n29. 
  40. ↑ "Action of proteolytic enzymes on lipotropins and endorphins: biosynthesis, biotransformation and fate". Pharmacology & Therapeutics 24 (3): 321–354. January 1984. doi:10.1016/0163-7258(84)90008-1. PMID 6087385. 
  41. ↑ "Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue". The European Journal of Neuroscience 20 (1): 92–100. July 2004. doi:10.1111/j.1460-9568.2004.03459.x. PMID 15245482. 
  42. ↑ „Electroacupuncture - an overview | ScienceDirect Topics“.
  43. ↑ „Biochemistry, Endorphin“, StatPearls. StatPearls Publishing, 2018. Qaraldi: 2019-yil 20-fevral. 
  44. ↑ "Understanding endorphins and their importance in pain management". Hawaii Medical Journal 69 (3): 70–71. March 2010. PMID 20397507. PMC 3104618. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3104618.  
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