Mechanism of action Д®ndorphins 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). Formation of О±-endorphin and Оі-endorphin results from proteolytic cleavage of ОІ-endorphin. Peptide convertase 2 (PC2) is responsible for cleaving ОІ-LPH into ОІ-endorphin and Оі-lipotropin. ОІ-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including О±-endorphin, ОІ-endorphin, and Оі-endorphin. In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and beta-lipotropin (ОІ-LPH). CPE facilitates POMC transport into immature budding vesicles. At the trans-Golgi network, POMC binds to a membrane-bound protein, carboxypeptidase E (CPE). All three types of endorphins are fragments of the precursor protein proopiomelanocortin (POMC). Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-OHД®ndorphin precursors are primarily produced in the pituitary gland. 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 Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH Some studies have characterized О±-endorphin activity as similar to that of psychostimulants and Оі-endorphin activity to that neuroleptics separately.

While ОІ-endorphin is studied for its opioid activity, О±-endorphin and Оі-endorphin both lack affinity for opiate receptors and thus do not affect the body in the same way that ОІ-endorphin does. О‘-endorphin and Оі-endorphin are primarily found in the anterior and intermediate pituitary. О±-endorphin has the shortest sequence, and ОІ-endorphin has the longest sequence. О±-endorphin and Оі-endorphin result from proteolytic cleavage of ОІ-endorphin between the Thr(16)-Leu(17) residues and Leu(17)-Phe(18) respectively. 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. The class of endorphins consists of three endogenous opioid peptides: О±-endorphin, ОІ-endorphin, and Оі-endorphin. Thus, endorphin is a contraction of 'endo(genous) (mo)rphin' (morphin being the old spelling of morphine). The word endorphin is derived from бј”ОЅОґОїОЅ / Greek: Г©ndon meaning 'within' ( endogenous, бјђОЅОґОїОіОµОЅО®П‚ / Greek: endogenes, 'proceeding from within'), and morphine, from Morpheus ( Ancient Greek: ОњОїПЃП†ОµПЌП‚, romanized: MorpheГєs), the god of dreams in the Greek mythology. Opioid peptides are classified based on their precursor propeptide: all endorphins are synthesized from the precursor proopiomelanocortin (POMC), encoded by proenkephalin A, and dynorphins encoded by pre-dynorphin. Studies have subsequently distinguished between enkephalins, endorphins, and endogenously-produced morphine, which is not a peptide. In addition, they found that it is completely removed from opiate receptors by naloxone, an identified morphine antagonist. Wilhelm Feldberg and Derek George Smyth in 1977 confirmed this claim, finding ОІ-endorphin to be much stronger than morphine. They identified that ОІ-endorphin produced strong analgesic effects.

In 1976, Choh Hao Li and David Chung recorded the sequences of О±-, ОІ-, and Оі-endorphin isolated from camel pituitary glands for their opioid activity. This term was essentially assigned to any peptide that demonstrated morphine-like activity. Simon, who independently discovered opioid receptors, would later term these peptides as endorphins. Snyder isolated morphine-like peptides from calf brain.

Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of morphine. 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. They isolated ' enkephalins' (from the Greek ОµОіОєОП†О±О»ОїП‚, cerebrum) from pig brain, identified as Met-enkephalin and Leu-enkephalin. Opioid peptides in the brain were first discovered in 1973 by investigators at the University of Aberdeen, John Hughes and Hans Kosterlitz.

Endorphin molecule