Neoendorphins

Definition
Neoendorphins are opioid peptides cleaved from prodynorphin. Alpha and beta-neoendorphins (a- and ß-NEO) are [Leu5] enkephalin segment - derived opioid peptides and ? and ?-type opioid receptor agonists1.

Related peptides
Post-translational processing of a precursor protein, prodynorphin yields 5 different opioid peptide products, a-NEO, ß-NEO, within the first COOH terminally extended [Leu5] enkephalin segment, Dynorphin (Dyn) A (1-17), its fragment, Dyn A (1-8) are present within the second segment. The third opioid segment in prodynorphin corresponds to the 13-amino acid peptide sequence, Dyn B. This prodynorphin-derived peptide family together with the proenkephalin products and pro-opiomelanocortin opioid products compose the three distinct groups of endogenous opioids1.

Discovery
a- Neoendorphin (aNEO) and ß-neoendorphin (ßNEO), originally described by Matsuo and co-workers in the 1980’s 2,3.

Structural Characteristics
a-NEO is an opiate decapeptide derived from the prodynorphin protein. The full sequence of a-NEO-endorphin has been determined to be:

Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys2.
ß-NEO is a nonapeptide whose complete amino acid sequence has been elucidated to be: Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro3.

Mode of Action
Dynorphins A and B and a-NEO appear to be the endogenous ligands for opioid ? receptors. The ? receptors are located predominantly in the cerebral cortex, nucleus accumbens, claustrum and hypothalamus of rat and mouse, and have been implicated in the regulation of nociception, diuresis, feeding, neuroendocrine and immune system functions. ß-NEO is an agonist of ?-receptors4.

Functions
Dynorphin and a -NEO bind to the K subtype of opioid receptors and have been shown to inhibit the release of noradrenaline from cardiac sympathetic axons. They play a important role in a number of physiological functions, including pain perception and responses to stress5.

References
1.Chavkin C, Bakhit C, Weber E, Bloom FE (1983). Relative contents and concomitant release of prodynorphin/neoendorphin-derived peptides in rat hippocampus. PNAS, 80(24):7669-7673.
2.Kangawa K, Minamino N, Chino N, Sakakibara S, Matsuo H (1981). The complete amino acid sequence of alpha-neo-endorphin. Biochem Biophys Res Comm.,. 99(3):871-878.
3.Minamino N, Kangawa K, Chino N, Sakakibara S, Matsuo H (1981). Beta-neo-endorphin, a new hypothalamic "big" Leu-enkephalin of porcine origin: its purification and the complete amino acid sequence. Biochem Biophys Res Commun., 99 (3):864-870.
4.Wegener K, Kummer W (1994). Sympathetic IMoradrenergic Fibers as the Source of Immunoreactive Alpha-Neoendorphin and Dynorphin in the Guinea Pig Heart. Acta Anat 151(2):112-119.
5.Book: Dentate Gyrus: a comprehensive guide to structure function and clinical implications By Helen. E. Scharfman.