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In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2020-Jan

Physiology, Enkephalin

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Joshua Cullen
Marco Cascella

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概要

The term opiate, or more appropriately opioids, is commonly referred to as a class of compounds, such as the alkaloids morphine, codeine, and thebaine, derived from the opium poppy (Papaver somniferum), and known and utilized by humankind for millennia for both analgesia and sedation. This class of substances also includes semi-synthetic compounds such as heroin, oxycodone, hydrocodone, and hydromorphone, obtained from these natural molecules as well as fully synthetic compounds, including fentanyl, pethidine, levorphanol, methadone, tramadol, and dextropropoxyphene. Morphine was first isolated in 1806, followed by the isolation of codeine several years later. Following the development of the hypodermic needle and hollow needle in the 1850s, physicians began to use morphine for various surgical procedures as well for the treatment of chronic pain and postoperative pain. With the discovery of different opioid agonists, antagonists, and partial agonist compounds such as nalorphine, various researches postulated and later proved that there are multiple stereospecific opioid binding sites in the central nervous system (CNS) through which they exert their physiological effects. Researchers further surmised that these receptors were most likely targets of endogenous opioid compounds, which researchers then began to isolate and study. In 1975, John Hughes and Hans Kosterlitz reported the first evidence of endogenous opioids in brain extracts that they noted were able to inhibit acetylcholine release from nerves in the guinea pig ileum. Further, they indicated that when treated with the opioid receptor antagonist naloxone, the inhibition was blocked. The compounds that they first isolated were termed enkephalins. Structurally, the enkephalins are pentapeptides that are distinguished in two subgroups by their carboxy-terminal amino acids, leucine, or methionine. As a consequence, the enkephalins either classify as met-encephalins and leu-encephalins, respectively: The enkephalins are one of the three peptide systems that also include beta-endorphins and dynorphins. Of note, the three classes of endogenous opioid peptides share a common N terminus sequence of Tyr-Gly-Gly-Phe and lack a C terminus amide. In molecular terms, Tyr and Phe bind the receptor, and the glycine pair acts as a spacer. These peptides act as neurotransmitters and neuromodulators throughout the nervous system and various end-organ targets. Additionally, research has found that met-enkephalin has an essential role in cell proliferation and tissue organization during development. When discussed in this context, met-enkephalin is often referred to as the opioid growth factor (OGF).

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