Endorphins (contracted from endogenous morphine)
History
in the brain were first discovered in 1973 by investigators at the University of Aberdeen, John Hughes and
Hans Kosterlitz. They isolated "
" (from the
Greek language εγκέφαλος) from
pig brain, identified as Met-enkephalin and Leu-enkephalin.
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.
Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of
morphine.
Rabi Simantov and Solomon H. Snyder isolated morphine-like peptides from calf brain.
Studies have subsequently distinguished between enkephalins, endorphins, and endogenously produced true morphine,
Etymology
The word
endorphin is derived from ἔνδον / meaning "within" (
endogenous, ἐνδογενής / , "proceeding from within"), and
morphine, from
Morpheus (), the god of dreams in the Greek mythology. Thus, endorphin is a contraction of 'endo(genous) (mo)rphin' (morphin being the old spelling of morphine).
Types
The class of endorphins consists of three endogenous opioid peptides: α-Endorphin, β-endorphin, and γ-endorphin.
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.
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.
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.
|
|
| 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 | |
| γ-Endorphin | Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH | |
Synthesis
Endorphin precursors are primarily produced in the
pituitary gland.
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).
CPE facilitates POMC transport into immature budding vesicles.
In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and
beta-lipotropin (β-LPH).
β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including α-endorphin, β-endorphin, and γ-endorphin.
Peptide convertase 2 (PC2) is responsible for cleaving β-LPH into β-endorphin and γ-lipotropin.
Formation of α-endorphin and γ-endorphin results from proteolytic cleavage of β-endorphin.
Regulation
Norepinephrine has been shown to increase endorphins production within inflammatory tissues, resulting in an
Analgesic;
the stimulation of sympathetic nerves by electro-acupuncture is believed to be the cause of its analgesic effects.
Mechanism of action
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.
Functions
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.
may also stimulate endorphin production and elevate one's pain threshold.
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".
See also
-
Neurobiological effects of physical exercise
-
Enkephalin
External links
