Endorphins (contracted from "endogenous morphine"[note 1]) are endogenous opioid neuropeptides and peptide hormones in humans and other animals. They are produced by the central nervous system and the pituitary gland. The term "endorphins" implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean "a morphine-like substance originating from within the body". The class of endorphins includes three compounds—α-endorphin (alpha endorphins), β-endorphin (beta endorphins), and γ-endorphin (gamma endorphins)—which preferentially bind to μ-opioid receptors. The principal function of endorphins is to inhibit the communication of pain signals; they may also produce a feeling of euphoria very similar to that produced by other opioids.
Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:
- John Hughes and Hans Kosterlitz of Scotland isolated – from the brain of a pig – what some called "enkephalins" (from the Greek εγκέφαλος, cerebrum).
- Around the same time, in a calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what Eric Simon (who independently discovered opioid receptors in vertebral brains) later termed "endorphin" by an abbreviation of "endogenous morphine", meaning "morphine produced naturally in the body". Studies have demonstrated that human and diverse animal tissues are capable of producing morphine, which is not a peptide. They have been continually researched for their pain relieving properties and role in the feeling of pleasure.
The three types of endorphins that exist are made through the fragmentation of precursor proteins. The original protein is called proopiomelanocortin (POMC). This protein is fragmented into many different smaller proteins including beta-lipotropin (β-LPH). β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides giving rise to α-Endorphin, β-Endorphin, γ-Endorphin and many other peptides.
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- α-Endorphin – The smallest fragment in the family and is composed of 16 amino acids. They are the same as the first 16 amino acids as the β-endorphin. The sequenced protein has been shown to be: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH.
- β-Endorphin – The longest fragment in the family and is composed of 31 amino acids. The sequence has been shown to be: 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 – The second longest fragment and is composed of 17 amino acids. It also matches the first 17 amino Acids of β-endorphin. The sequence has been shown to be: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OH.
Mechanism of action
Endorphins are naturally produced in response to pain. This phenomenon happens in both the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). In the PNS, endorphins, primarily β-endorphin, are released from the pituitary gland and bind to μ-receptors. The binding of these two components inhibits the pain signal of the periphery nerves by blocking the neurotransmitter substance P. The mechanism in the CNS is similar but works by blocking a different neurotransmitter. When the endorphin binds to the μ-receptor, it inhibits the release of the neurotransmitter gamma-aminobutyric acid (GABA) which, in turn, increases the production and release of dopamine, the neurotransmitter associated with pleasure.
Their production can also be triggered by various human activities. Vigorous aerobic exercise can stimulate the release of β-endorphin which contributes to a phenomenon known as a "runner's high."
Laughter may also stimulate endorphin production; a 2011 study showed that attendees at a comedy club showed increased resistance to pain. Endorphins are also released during various activities including eating food, sex, orgasm, listening to music and eating chocolate. Research has also demonstrated meditation by trained individuals to trigger endorphin release. 
Endorphins play a major role in the body's response to inhibiting pain but endorphins have also been looked at for their role in pleasure. There has been a lot of research in the euphoric state that is produced after the release of endorphins in cases such as runner's high, orgasms, and eating appetizing food. Endorphins have also been looked into as a way to aid in the treatment of anxiety and depression through exercising.
On the other hand, endorphins may also be involved in exercise addiction. The release of endorphins a person gets while exercising will produce a feeling of euphoria. With consistent exercise, the brain may down-regulate the production of endorphins in periods of rest and a person will need to continue to exercise more intensely in order to receive the same feeling.
From the words ἔνδον / Greek: éndon meaning "within" (endogenous, ἐνδογενής / Greek: endogenes, "proceeding from within") and morphine, from Morpheus (Ancient Greek: Μορφεύς, romanized: Morpheús), the god of dreams in the Greek mythology, thus 'endo(genous) (mo)rphin’ (morphin being the old spelling of morphine).
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Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. ... The apparently serendipitous finding of an opiate alkaloid-sensitive, opioid peptide-insensitive, µ3 opiate receptor subtype expressed by invertebrate immunocytes, human blood monocytes, macrophage cell lines, and human blood granulocytes provided compelling validating evidence for an autonomous role of endogenous morphine as a biologically important cellular signalling molecule (Stefano et al., 1993; Cruciani et al., 1994; Stefano and Scharrer, 1994; Makman et al., 1995). ... Human white blood cells have the ability to make and release morphine
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Comments: β-Endorphin is the highest potency endogenous ligand ... Morphine occurs endogenously .
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