Endorphin Là Gì

[Yury Morris]

Endorphins (contracted from endogenous morphine)[1][2][3] are peptides produced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in the pituitary gland of the brain. Endorphins are endogenous painkillers often produced in the brain and adrenal medulla during physical exercise or orgasm and inhibit pain, muscle cramps, and relieve stress.[4][5][6][7]

Opioid peptides in the brain were first discovered in 1973 by investigators at the University of Aberdeen, John Hughes and Hans Kosterlitz. They isolated "enkephalins" (from the Greek εγκέφαλος, cerebrum) from pig brain, 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-relieving analgesic effects of morphine and 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 of morphine.[11][12]

Rabi Simantov and Solomon H. Snyder isolated morphine-like peptides from calf brain.[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 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.[19]

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced morphine,[20][21] 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.[12][22]

The class of endorphins consists of three endogenous opioid peptides: α-endorphin, β-endorphin, and γ-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]

Endorphin precursors are primarily produced in the pituitary gland.[29][30][31] All three types of endorphins are fragments of the precursor protein proopiomelanocortin (POMC). At the trans-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 into adrenocorticotropin (ACTH) and beta-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]

Noradrenaline has been shown to increase endorphins production within inflammatory tissues, resulting in an analgesic effect;[36] the stimulation of sympathetic nerves by electro-acupuncture is believed to be the cause of its analgesic effects.[37]

Endorphins are released from the pituitary gland, typically in response to pain, and can act in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the PNS, β-endorphin is the primary endorphin released from the pituitary gland. Endorphins inhibit transmission of pain signals by binding μ-receptors of peripheral nerves, which block their release of neurotransmitter substance 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 of dopamine, a neurotransmitter associated with reward learning.[27][38]

Endorphins play a major role in the body's inhibitory response to pain. Research has demonstrated that meditation by trained individuals can be used to trigger endorphin release.[39][failed verification] Laughter may also stimulate endorphin production and elevate one's pain threshold.[40]

Endorphin production can be triggered by vigorous aerobic exercise. The release of β-endorphin has been postulated to contribute to the phenomenon known as "runner's high".[41][42] However, several studies have supported the hypothesis that the runner's high is due to the release of endocannabinoids rather than that of endorphins.[43] Endorphins may contribute to the positive effect of exercise on anxiety and depression.[44] The same phenomenon may also play a role in exercise addiction. Regular intense exercise may cause the brain to downregulate the production of endorphins in periods of rest to maintain homeostasis, causing a person to exercise more intensely in order to receive the same feeling.[45]

Endorphins are the body's natural painkillers. Released by the hypothalamus and pituitary gland in response to pain or stress, this group of peptide hormones both relieves pain and creates a general feeling of well-being.

About 20 different types of endorphins exist. The best studied of these is beta-endorphin, which is the one associated with the runner's high. We also release endorphins when we laugh, fall in love, have sex, and even eat a delicious meal.

Endogenous morphine, coined by the morphing of the two descriptive terms into endorphins, are opioid neuropeptides that are naturally produced in the body that serve a primary function as an agent blocking the perception of pain and, additionally, present in cases of pleasure. Historically, morphine receptors were discovered in the nervous system before the discovery and understanding of endorphins. This natural receptor spoke to the possibility of the existence and effect of endorphins that was later confirmed.

Endorphins were discovered to not only display functions as neurotransmitters in the central nervous system but additionally as peptide hormones released into the circulatory system by the pituitary gland. Endorphins have been linked clinically to cases of mental issues, including autism, depression, and depersonalization disorder, as well as to activities such as laughter and vigorous aerobic exercise.[1][2][3]

The origins of endorphins have been traced to the precursor pro-opiomelanocortin (POMC) polypeptide, which is synthesized in the pituitary gland. Recent studies have produced evidence suggesting that POMC may also be produced by the immune system and, consequently, also provide a base source for endorphin production. POMC consists of a 241 amino acid chain which is cleaved by enzyme (prohormone convertases) action into the 93 amino acid single-chain polypeptide beta-lipoprotein (beta-LPH). Beta-LPH is cleaved via enzymes into beta-melanocyte-stimulating hormone and endorphins, amongst other molecule types. Endorphins are identified as three distinct peptides termed alpha-endorphins, beta-endorphins, and gamma-endorphins. The beta-endorphins are the longest chain, containing 31 amino acids in the following sequence: 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. This sequence corresponds to amino acids 104 to 134 in the sequence of beta-LPH. The second-longest chain is the gamma-endorphins, consisting of a 17 amino acid chain the same as the first 17 amino acid chain sequence of the beta-endorphins. Finally, the third and shortest type of endorphins about the amino acid chain sequence is the alpha-endorphins. The alpha-endorphins are amino acid chains comprised of the same first 16 amino acid sequence as the beta-endorphins (and consequently has the same sequence of the first 16 amino acids comprising the gamma-endorphins). Thus, the sequences of beta-endorphins and gamma-endorphins essentially have the sequence of alpha-endorphins nested within them. This molecular configuration thereby allows these endorphins to be the agonist of opioid receptors, the same receptors to which chemicals derived from opium, such as morphine, bind to for triggering physiological responses.[4][5][6]

The mechanism of endorphins can be viewed through two different lenses through activity in the peripheral nervous system (PNS) and the CNS. In the PNS, the perception of pain relief is produced beta-endorphins bind to opioid receptors. Opioid receptors are broken down into four primary classes of G protein-coupled receptors: mu-receptors, delta-receptors, kappa-receptors, and nociceptin receptors. The greatest binding potential exists between the beta-endorphins and the mu-receptors. Mu-receptors can be found throughout the nerves of the PNS. When this beta-endorphin to mu-receptor binding occurs on nerve terminals (happening pre-synaptically or post-synaptically), analgesic effects are realized. The effects are realized as the aforementioned binding results in triggering of chemical events preventing the release of substance P, amongst other tachykinins, which is an instrumental undecapeptide in the conveyance of pain. Just as beta-endorphin to mu-opioid binding occurs in the peripheral nervous system, it also occurs in the central nervous system. There is a difference, though, as the mechanism triggered by the binding opposes the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) as opposed to substance P. With this suppression of GABA, the result is an increase in production and action of dopamine, the pleasure, and reward-associated neurotransmitter.

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