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Endorphins

Endorphins


Endorphins are small neuropeptides that are produced by the body and act to reduce painhence, the name endorphin (a shortened version of endogenous morphine). The term "enkephalin" (meaning literally "in the head") is also applied to endorphins, but usually refers to smaller molecules that have pain-relieving properties.

Endorphins were discovered when scientists found sites where molecules such as morphine bind to nerve cells and reasoned that the body must use these sites to bind chemical compounds. Experiments showed that the compounds were small peptides, and the actions of endorphins were determined by a number of researchers.

Although similar in primary structure to proteins, endorphins are smaller, ranging from five to forty or more amino acids in length. Endorphins are not considered to be neurotransmitter molecules, but are instead classified as neuromodulatory, that is, they modify the action of neurotransmitters through a number of effects associated with pain or pleasure.

Protein molecules are often synthesized in long chains by the body and cut apart to form functional individual protein units. β -endorphin molecules are produced by the body as portions of larger proopiomelanocortin (POMC) molecules, which are coded for by a single gene, synthesized as large molecules, and then cut by enzymes into active subunits. POMC also contains several hormones. The β -endorphin molecules function to relieve pain or produce pleasurable feelings and contain within their structure the pentapeptides met-enkephalin and leu-enkephalin. Composed of five amino acids joined by amide linkages, met-enkephalin (see Figure 1) and leuenkephalin (see Figure 2) differ only in the amino acid present at the carboxylic acid (C-terminal) end.

A wide range of physiological effects has been observed for endorphins, but the ultimate function and number of endorphins may not yet be known. Endorphins exhibit a number of neurological effects associated with the relief of pain. The administration of exogenous endorphins (those prepared outside the body) stimulates the release of many other hormones including prolactin, adrenocorticotropic hormone (ACTH), and antidiuretic hormone. The analgesic effects of morphine are commonly believed to be caused by binding to receptor sites for endorphins, but few beneficial effects of treatment with exogenous endorphins have been reported.

Early speculations concerning the function of endorphins suggested that they were natural painkillers that the body produced to alleviate pain in circumstances requiring an individual to continue functioning in spite of injury or stress. Examples of such situations might include childbirth, exercise, and combat. In addition to affecting one's perception of pain, endorphins may be involved in other phenomena such as runner's high and acupuncture. Persons who exercise regularly have higher than usual amounts of β -endorphin

in their bloodstream, and the levels of β -endorphin molecules increase during exercise, perhaps accounting for the enhanced feelings of well-being experienced by long-distance runners. Acupuncturists insert and manipulate long needles at precise locations on the skin. After insertion of the needles, patients experience a reduction in pain or may have other physiological responses. In some cases, the stimulation of these acupuncture points by massage may result in the release of endorphins into the blood. Practices such as squeezing the upper lip to stifle a sneeze or massaging the fleshy area between the thumb and forefinger to alleviate a headache may be related to endorphin effects.

Healthy humans are able to overcome stress and pain, allowing them to continue functioning without being overcome by either. To some degree the response is probably psychological, but evidence that the endorphin effect is real exists in the relationship of the opioid-like drug naloxone to the placebo effect. Given a placebo (a so-called sugar pill), many patients report a decrease in pain. The placebo effect is reduced if naloxone, a drug used to treat the intoxicating effects of narcotics, is administered. The administration of naloxone also reduces the endorphin effect; if given naloxone, patients report increased sensitivity to pain. In addition, abnormal levels of endorphins may be associated with mental illness such as autism or depression. For example, an autistic patient might produce so much endogenous endorphin that he or she does not need to react to the world outside, and a depressed person might not produce enough endorphin to withstand the pain and pressures of daily life.

see also Neurotransmitters; Peptide Bond.

Dan M. Sullivan

Bibliography

Devlin, Thomas M., ed. (2002). Textbook of Biochemistry: With Clinical Correlations, 5th edition. New York: Wiley-Liss.

McKee, Trudy, and McKee, James R. (2003). Biochemistry: The Molecular Basis of Life, 3rd edition. Boston: McGraw-Hill.

Snyder, S. (1986). Drugs and the Brain. New York: W.H. Freeman.

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Sullivan, Dan M.. "Endorphins." Chemistry: Foundations and Applications. 2004. Encyclopedia.com. 29 Aug. 2016 <http://www.encyclopedia.com>.

Sullivan, Dan M.. "Endorphins." Chemistry: Foundations and Applications. 2004. Encyclopedia.com. (August 29, 2016). http://www.encyclopedia.com/doc/1G2-3400900172.html

Sullivan, Dan M.. "Endorphins." Chemistry: Foundations and Applications. 2004. Retrieved August 29, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3400900172.html

endorphins

endorphins During the 1960s and early 1970s, it became apparent that opioid drugs such as morphine and heroin produced their profound actions in the body by interacting with specific receptors on the outer membrane of nerve cells. This raised the intriguing question of why the body goes to the trouble of synthesizing such receptor proteins. Surely it was not just on the off chance that a drug such as morphine might be administered. In 1975 the group in Aberdeen, Scotland led by Hans Kosterlitz and John Hughes, isolated from the pig brain two related molecules, the enkephalins, which bind to and activate opioid receptors. These enkephalins are short peptides, each comprising five amino acids. Although at first glance the enkephalins did not look similar in chemical composition to morphine, they proved to have a crucial component in common. We now know that the brain contains as many as thirteen such endogenous (internally generated) opioid peptides, which have come to be referred to collectively as ‘endorphins’.

There are three classically defined opioid receptor types, named the m, d, and k receptors, and each of the endorphins shows a different spectrum of activation (agonist action) at these different receptors. The endorphins function as inhibitory neurotransmitters and neurohormones: they are released from nerve cells to act on other cells that bear opioid receptors and thus dampen the activity of those cells.

To probe the physiological functions of the endogenous opioid systems, either antagonist drugs can be administered or transgenic mice lacking one or more of the receptors can be developed. From such studies it is evident that the endorphins play little part in our normal routine daily functions. If, in ordinary circumstances, one were to be given an opioid antagonist such as naloxone, little change would be observed. It is when the body is stressed that the endorphins are important. Then they are released to activate their receptors and help to protect the body. Thus endorphins interacting with the m and d receptors have been implicated in the inability of some accident victims to sense the severe pain that their injuries should be causing and also in the ‘high’ that is experienced following exercise. Endogenous opioids may also be responsible for part of the analgesia experienced during acupuncture therapy.

Recently a new, endogenous neuropeptide system, very closely associated with the endogenous opioid system, has been discovered. Unfortunately, at present the terminology used to label the receptor and its endogenous peptide agonist is still quite clumsy. The receptor is referred to as the ORL1 receptor, and the endogenous peptide that is an agonist at the receptor is called either nociceptin or orphanin FQ. The term ‘nociceptin’ derives from the initial belief that this peptide acts in the opposite direction to the endorphins in that, rather than being pain relieving, it actually enhances pain (cf. noxious, from the Latin noceo, to injure). It is becoming apparent that this is an oversimplification and that this peptide in some circumstances inhibits the action of morphine and the endorphins but in other circumstances can also itself suppress pain.

What is very exciting is that this new system appears to be involved in other important brain functions apart from the sensation of pain. The discovery that it may be involved in memory, anxiety, and appetite control make it an exciting new area for drug development. Several major pharmaceutical companies are currently developing non-peptide molecules (more stable and brain-penetrating than the peptides) that will act as agonists and antagonists at the ORL1 receptor, to advance our knowledge of the physiological and pathophysiological functions of this receptor. Hopefully this will result in the discovery of novel therapeutic agents.

G. Henderson


See also analgesia; opiates and opioid drugs; membrane receptors; peptides.

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COLIN BLAKEMORE and SHELIA JENNETT. "endorphins." The Oxford Companion to the Body. 2001. Encyclopedia.com. 29 Aug. 2016 <http://www.encyclopedia.com>.

COLIN BLAKEMORE and SHELIA JENNETT. "endorphins." The Oxford Companion to the Body. 2001. Encyclopedia.com. (August 29, 2016). http://www.encyclopedia.com/doc/1O128-endorphins.html

COLIN BLAKEMORE and SHELIA JENNETT. "endorphins." The Oxford Companion to the Body. 2001. Retrieved August 29, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O128-endorphins.html

endorphins

endorphins (ĕndôr´fĬnz), neurotransmitters found in the brain that have pain-relieving properties similar to morphine. There are three major types of endorphins: beta endorpins, found primarily in the pituitary gland; and enkephalins and dynorphin, both distributed throughout the nervous system. Endorphins interact with opiate receptor neurons to reduce the intensity of pain: among individuals afflicted with chronic pain disorders, endorphins are often found in high numbers. Many painkilling drugs, such as morphine and codeine, act like endorphins and actually activate opiate receptors. Besides behaving as a pain regulator, endorphins are also thought to be connected to physiological processes including euphoric feelings, appetite modulation, and the release of sex hormones. Prolonged, continuous exercise contributes to an increased production and release of endorphins, resulting in a sense of euphoria that has been popularly labeled "runner's high."

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endorphin

endorphin Any of a group of substances, found naturally in brain and other tissues, that have pain-relieving effects similar to those of morphine. They are all peptides or polypeptides and include the encephalins, which consist of five amino acids and occur principally in the brain. Several endorphins are associated with the pituitary, while others occur in various body tissues, including the placenta, adrenal glands, and pancreas.

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endorphin

endorphin (endogenous morphine) Naturally occurring peptide neurotransmitter found in the pituitary gland that has similar pain-relieving effects as morphine and other derivatives of opium. Endorphins block the sensation of pain by binding to pain-receptor sites. Two endorphins (enkephalins) occur in the brain, spinal cord and gut. See also analgesic; neuron; neurotransmitter

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endorphin

en·dor·phin / enˈdôrfin/ • n. Biochem. any of a group of hormones secreted within the brain and nervous system that activate the body's opiate receptors, causing an analgesic effect.

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endorphins

endorphins Peptides, peculiar to vertebrates, manufactured by the pituitary gland, which have analgesic properties similar to opiates (e.g. morphine), because of an affinity for the same receptors in the brain.

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endorphin

endorphin (en-dor-fin) n. one of a group of peptides that occur naturally in the brain and have pain-relieving properties similar to those of the opiates. See also encephalin.

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endorphin

endorphin •Aladdin • stand-in •Dunedin, lead-in •Blondin, Girondin •Odin •paladin, Saladin •Borodin • Baffin • elfin •biffin, griffin, tiffin •boffin, coffin •dolphin • endorphin • bowfin •yellowfin •muffin, puffin •ragamuffin • paraffin • perfin •bargain • Begin • Kosygin •hoggin, noggin •imagine • margin • engine •pidgin, pigeon, smidgen, wigeon •stool pigeon • wood pigeon • origin •Pugin • virgin

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