Endorphins

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Endorphins are the body's own opioid peptides that are produced in the pituitary gland and hypothalamus of vertebrates . Endorphins arise as the breakdown products of three precursor proteins - namely, they become

The word endorphin is a word crossing from end ogenes M Orphin to mean a self-produced by the body opioid '.

Discovery story

Opiates and opioids belong to a defined group of substances that are of great importance because of their pain-relieving effect and whose abuse also leads to dependence. As abuse increased in the US and Western countries from the mid-1960s, efforts were made to elucidate the mechanism of action of opioids. At that time, the researchers were looking for the natural ligands , which were then independently detected in 1973 by Solomon H. Snyder , Candace B. Pert , Lars Terenius and others. The exogenously administered opioids also docked to these opioid receptors in the brain . Demonstrated were the endorphins finally in 1975 by the Scottish researchers John Hughes and Hans Kosterlitz in the midbrain of the pig. The first common name was therefore also Enkephaline (from the Greek word en-kephalos, "in the head").

chemistry

Chemically speaking, they are short neuropeptides that bind to opioid receptors . A common structural feature of endorphins is a peptide group with four amino acids (tetrapeptide) of the sequence tyrosine - glycine-glycine - phenylalanine (in the example below bold). The first opioid peptides to be synthesized in the laboratory were methionine-enkephalin and leucine-enkephalin.

Amino acid sequences of

  • α-Endorphin: Tyr-Gly-Gly-Phe- Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH
  • 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-OH.
  • γ-endorphin: Tyr-Gly-Gly-Phe- Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH

physiology

Endorphins regulate sensations such as pain ( algesia ) and hunger . They are related to the production of sex hormones and are made responsible for the development of euphoria . The endorphin system is activated , among other things, in emergency situations. Up until now it was assumed that the release of endorphins is the reason why some seriously injured people do not feel any pain at first . More recent findings indicate that the beta-endorphin (1-31) released from the pituitary gland into the free bloodstream binds to opioid receptors, but does not mediate analgesia. However, this does not rule out that beta-endorphin (1-31) in other media (liquor, tissues) could have an analgesic component (this has not yet been shown explicitly).

Certain physical exertion (see Runner's High ) and pain experiences can possibly induce a feeling of happiness through the release of endorphins. This effect is medically recognized in the meantime, even if it is experienced very differently.

Effect, receptors

Opioid receptors for endorphins and other opioids can be found in the gray matter of the spinal cord , for example . They can also be found on vegetative synapses and other areas of the brain. Opioid receptors are likely to exist even in peripheral structures such as joints.

In the spinal cord, when the endorphin receptors are excited, a pain stimulus is suppressed when it arrives via the afferent nerves in the spinal cord and is to be switched over and forwarded to the brain.

The exact mechanism of action of the endorphins has not yet been clarified in all details. But it is known that endorphins can manipulate dopaminergic conduction. The release of dopamine into the synaptic gap is increased.

See also

Proopiomelanocortin derivatives
POMC
     
γ-MSH ACTH β-lipotropin
         
  α-MSH CLIP γ-lipotropin β-endorphin
       
    β-MSH  

literature

  • Josef Zehentbauer: The body's own drugs . Artemis Winkler Verlag, 2003, ISBN 3-491-69410-8 .
  • Solomon H. Snyder: Brainstorming: the science and politics of opiate research . Harvard University Press, Cambridge, Mass. 1989, ISBN 0-674-08048-3 .
  • H. Harbach, K. Hell et al .: Beta-endorphin (1-31) in the plasma of male volunteers undergoing physical exercise. In: Psychoneuroendocrinology . Volume 25, Number 6, August 2000, ISSN  0306-4530 , pp. 551-562. PMID 10840168 .

Individual evidence

  1. ^ Hughes J: Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine . In: Brain Res. . 88, No. 2, May 1975, pp. 295-308. PMID 1148827 .
  2. ^ Hughes J, Smith T, Morgan B, Fothergill L: Purification and properties of enkephalin - the possible endogenous ligand for the morphine receptor . In: Life Sci . 16, No. 12, June 1975, pp. 1753-8. PMID 1152599 .
  3. ↑ Kosterlitz HW, Hughes J: Some thoughts on the significance of enkephalin, the endogenous ligand . In: Life Sci . 17, No. 1, July 1975, pp. 91-6. PMID 806763 .
  4. ^ Pert CB, Snyder SH: Opiate receptor: demonstration in nervous tissue . In: Science . 179, No. 77, March 1973, pp. 1011-4. PMID 4687585 .
  5. ^ Terenius L: Characteristics of the "receptor" for narcotic analgesics in synaptic plasma membrane fraction from rat brain . In: Acta Pharmacol Toxicol . 33, No. 5, 1973, pp. 377-84. PMID 4801083 .
  6. ↑ a b Ling N, Burgus R, Guillemin R: Isolation, primary structure, and synthesis of alpha-endorphin and gamma-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity . In: Proc. Natl. Acad. Sci. USA . 73, No. 11, November 1976, pp. 3942-6. PMID 1069261 . PMC 431275 (free full text).
  7. ↑ Dragon N, Seidah NG, Lis M, Routhier R, Chrétien M: Primary structure and morphine-like activity of human beta-endorphin . In: Can. J. Biochem. . 55, No. 6, June 1977, pp. 666-70. PMID 195688 .
  8. ↑ Szechtman H, Hershkowitz M, Simantov R: Sexual behavior decreases pain sensitivity and stimulated endogenous opioids in male rats . In: Eur J Pharmacol . 70, No. 3, March 1981, pp. 279-85. PMID 6262094 .
  9. ↑ Matejec R, Uhlich H, Hotz C, et al. : Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin (1-31), but does not reduce heat pain sensitivity . In: Neuroendocrinology . 82, No. 3-4, 2005, pp. 185-97. doi : 10.1159 / 000091980 . PMID 16534240 .
  10. ↑ Matejec R, Harbach HW, Bödeker RH, Hempelmann G, Teschemacher H: Plasma levels of corticotroph-type pro-opiomelanocortin derivatives such as beta-lipotropin, beta-endorphin (1-31), or adrenocorticotropic hormone are correlated with severity of postoperative pain . In: Clin J Pain . 22, No. 2, February 2006, pp. 113-21. PMID 16428944 .
  11. ↑ Boecker H, Sprenger T, Spilker ME, et al. : The runner's high: opioidergic mechanisms in the human brain . In: Cereb. Cortex . 18, No. 11, November 2008, pp. 2523-31. doi : 10.1093 / cercor / bhn013 . PMID 18296435 .
  12. ^ Cohen EE, Ejsmond-Frey R, Knight N, Dunbar RI: Rowers' high: behavioral synchrony is correlated with elevated pain thresholds . In: Biol. Lett. . 6, No. 1, February 2010, pp. 106-8. doi : 10.1098 / rsbl.2009.0670 . PMID 19755532 .
  13. ^ Pestell RG, Hurley DM, Vandongen R: Biochemical and hormonal changes during a 1000 km ultramarathon . In: Clin. Exp. Pharmacol. Physiol. . 16, No. 5, May 1989, pp. 353-61. PMID 2548778 .
  14. ↑ Matejec R, Schulz A, Mühling J, et al. : Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain? . In: Neuropeptides . 40, No. 1, February 2006, pp. 11-21. doi : 10.1016 / j.npep.2005.10.001 . PMID 16289330 .

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