Endorphins are endogenous opioid biochemical compounds. They are peptides produced by the pituitary gland and the hypothalamus in vertebrates, and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. In other words, they might work as "natural pain killers."

The term "endorphin" implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation.

History

These opioid neuropeptides were first discovered in 1975 by two independent groups of investigators. John Hughes and Hans Kosterlitz of Scotland isolated --- from the brain of a pig --- what they called "enkephalins" (from the Greek εγκέφαλος, "cerebrum"). Around the same time in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what they later termed "endorphin", an abbreviation of "endogenous morphine", which literally means "morphine produced naturally in the body". In fact, morphine itself is not a peptide, and although it is produced by some plants (the opium poppy) it is not produced by animals.

Molecular biology

There are at least three different families of opioid peptides.

The amino acid residue sequence (primary structure) of β-endorphin is: 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-GluOH (Fries, 2002).

Other opioid peptides are the enkephalins and the dynorphins. The term enkephalin mainly refers to two peptides, -enkephalin and -enkephalin, which are both products of the proenkephalin gene. -enkephalin is Tyr-Gly-Gly-Phe-Met. -enkephalin has Leu in place of Met. Dynorphin is the product of a third opioid gene, called prodynorphin.

Mechanism of action

Beta-endorphin is released into the blood (from the pituitary gland) and into the spinal cord and brain from hypothalamic neurons. The beta-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood-brain barrier. The physiological importance of the beta-endorphin that can be measured in the blood is far from clear: beta-endorphin is a cleavage product of POMC which is the precursor hormone for adrenocorticotrophic hormone (ACTH), so it will be released whenever ACTH is released. The behevioral effects of beta-endorphin are exerted by its actions in the brain and spinal cord, and

Beta-endorphin has the highest affinity for the Mu1-opioid receptor, slightly lower affinity for the Mu2 and Delta-opioid receptors and low affinity for the Kappa1-opioid receptors. Mu receptors are the main receptor through which morphine acts. Classically, Mu receptors are presynaptic, and inhibit neurotransmitter release; through this mechanism, they inhibit the release of the inhibitory neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and lead to aberrant synaptic plasticity which causes addiction. Opioid receptors have many other and more important roles in the brain and periphery however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation, and receptors are often found at postsynaptic locations as well as presynaptically.

Activity

Scientists debate whether specific activities release measurable levels of endorphins. Much of the current data comes from animal models which may not be relevant to humans. The studies that do involve humans often measure endorphin plasma levels, which do not necessarily correlate with levels in the CNS. Other studies use an opioid antagonist, usually naloxone, to indirectly measure the release of endorphins by observing the changes that occur when any endorphin activity that might be present is blocked.

Capsaicin (the active chemical in chili peppers) also has been shown to stimulate endorphin release. Topical capsaicin has been used as a treatment for certain types of chronic pain.

References

• Altman, Nathaniel. “Endorphins Q & A.” 2002. <>.
• Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye's Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.
• Goldberg, Jeff (1988). Anatomy of a Scientific Discovery. Bantam Books, 1988. ISBN 0553346318; ISBN 0553176161 (British edition); ISBN 0553052616 (hardcover).
• Groopman, Jerome. The Anatomy of Hope. New York: Random House, 2004. 169-173.
• Klosterman, Lorrie. “Endorphins: The Gift You Give Yourself.” Chronogram. Nov 2005. <>.
• Margolis, Simeon. The Johns Hopkins Medical Handbook. New York, NY: Redley, 1995. 140-141.
• Simantov, R. & Snyder, H. (1976). Morphine-like peptides in mammalian brain: Isolation, structure elucidation, and interactions with the opiate receptor. Proceedings of the National Academy of Sciences (USA), 73: 2515, 1976.
• Smith, Trenton & Tasnadi, Attila (2003). A Theory of Natural Addiction <>

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