Enkephalin

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Contents

General function

Enkephalins were the first reported evidence of endogenous opioids in the brain, by John Hughes and Hans Kosterlitz in 1975 [1] [2]. They are pentapeptides that can be divided into two groups based on their carboxy-terminal amino acids: methionine-enkephalin and leucine-enkephalin. Enkephalin acts as a neurotransmitter through opioid receptors, more specifically through the classical opioid receptor δ [3]. The main functions of enkephalins include analgesia, but they are also involved in the control of respiratory, cardiovascular and gastrointestinal functions, and participate in neuroendocrine regulation [4] [5] [6].

Enkephalin is generated from the cleavage of the precursor pro-enkephalin, resulting in Met-enkephalin or Leu-enkephalin. The processing of one molecule of pro-enkephalin generates six copies of Met-enkephalin and one copy of Leu-enkephalin [3].

Enkephalin is mainly distributed throughout the central, peripheral and autonomic nervous system in mammals [3]. However, opioid receptors are broadly distributed in the body, such as the cardiac and gastrointestinal systems.


Physiological functions

Analgesia

Enkephalins belong to one of the four major families of endogenous opioid ligands [7]. Opioid receptors couple to inhibitory G proteins and when they are activated Gα and Gβγ subunits dissociate and induce a signaling cascade that leads to a reduced neurotransmitter release [7]. All four opioid receptors inhibit N-, P/Q- and L-type voltage-gated calcium channels [7] [8] by the Gβγ subunit, which inhibits the entry of calcium to the pre-synaptic neuron, preventing the fusion of calcium-dependent synaptic vesicules with the membrane terminal and therefore blocking the neurotransmitter release. Transmission of pain signals is thus blocked. Enkephalins can be released from infiltrating immune cells at the site of injuries and from neurons in the central nervous system [7].

Stress response regulation

Pathophysiology

Structure

Clinical relevance

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References

  1. ↑ John Hughes, Terry Smith, Barry Morgan, Linda Fothergill, Purification and properties of enkephalin — The possible endogenous ligand for the morphine receptor, Life Sciences, Volume 16, Issue 12,1975,Pages 1753-1758,ISSN 0024-3205,https://doi.org/10.1016/0024-3205(75)90268-4.
  2. ↑ Hans W. Kosterlitz, John Hughes, Some thoughts on the significance of enkephalin, the endogenous ligand, Life Sciences, Volume 17, Issue 1, 1975, Pages 91-96, ISSN 0024-3205, https://doi.org/10.1016/0024-3205(75)90243-X.
  3. ↑ 3.0 3.1 3.2 Cullen JM, Cascella M. Physiology, Enkephalin. [Updated 2021 Mar 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557764/
  4. ↑ Marcotte, I., Separovic, F., Auger, M., & Gagné, S. M. (2004). A multidimensional 1H NMR investigation of the conformation of methionine-enkephalin in fast-tumbling bicelles. Biophysical journal, 86(3), 1587–1600. https://doi.org/10.1016/S0006-3495(04)74226-5
  5. ↑ Cesselin, F. 1997. Endomorphines, Récepteurs des Opioïdes et Nociception. In Douleurs: Bases Fondamentales, Pharmacologie, Douleurs Aiguës, Douleurs Chroniques, Thérapeutiques. L. Brasseur, M. Chauvin, G. Guilbaud, and P. Guesnon, editors. Maloine, Paris, France.
  6. ↑ Fuxe, K., Borroto-Escuela, D. O., Romero-Fernandez, W., Diaz-Cabiale, Z., Rivera, A., Ferraro, L., Tanganelli, S., Tarakanov, A. O., Garriga, P., Narváez, J. A., Ciruela, F., Guescini, M., & Agnati, L. F. (2012). Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks. Frontiers in physiology, 3, 136. https://doi.org/10.3389/fphys.2012.00136
  7. ↑ 7.0 7.1 7.2 7.3 Corder, G., Castro, D. C., Bruchas, M. R., & Scherrer, G. (2018). Endogenous and Exogenous Opioids in Pain. Annual review of neuroscience, 41, 453–473. https://doi.org/10.1146/annurev-neuro-080317-061522
  8. ↑ Rusin, K. I., Giovannucci, D. R., Stuenkel, E. L., & Moises, H. C. (1997). Kappa-opioid receptor activation modulates Ca2+ currents and secretion in isolated neuroendocrine nerve terminals. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17(17), 6565–6574. https://doi.org/10.1523/JNEUROSCI.17-17-06565.1997

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