Title: Dynorphin
CAS Registry Number: 74913-18-1
Literature References: Extremely potent, widely distributed neuropeptide that has 17 amino acid residues and contains leu5-enkephalin as its NH2-terminal sequence. Its name is derived from "dynamis", the Greek word for power, and endorphin, the name applied to the group of opioid peptides to which it belongs. Initially isolated from porcine pituitaries and termed slow-reversing endorphin: L. I. Lowney et al., Life Sci. 24, 2377 (1979). Purification, description of properties and amino acid sequence of the first 13 residues: A. Goldstein et al., Proc. Natl. Acad. Sci. USA 76, 6666 (1979). Complete amino acid sequence of the heptadecapeptide from porcine pituitary: eidem, ibid. 78, 7219 (1981). Isoln from porcine duodenum and identity with pituitary dynorphin: S. Tachibana et al., Nature 295, 339 (1982). Synthesis of porcine dynorphin1-13: M. Wakimasu et al., Chem. Pharm. Bull. 29, 2592 (1981). Soln conformation: R. Maroun, W. L. Mattice, Biochem. Biophys. Res. Commun. 103, 442 (1981). Radioimmunoassay: V. E. Ghazarossian et al., Life Sci. 27, 75 (1980). Comparison of distribution of dynorphin and enkephalin systems in brain: S. J. Watson et al., Science 218, 1134 (1982). Behavioral effects of dynorphin1-13 in mice and rats: J. M. Walker et al., Peptides 1, 341 (1980); H. Zwiers et al., Life Sci. 28, 2545 (1981). Opiate activity and receptor selectivity: M. Wuester et al., Neurosci. Lett. 20, 79 (1980); C. Chavkin, A. Goldstein Nature 291, 591 (1981). In the guinea pig ileum bioassay it has been shown to be 700 times more potent than leu5-enkephalin and its agonist effects are 1/13th as sensitive to naloxone antagonism: eidem, Proc. Natl. Acad. Sci. USA 78, 6543 (1981). Dynorphin1-13 has been proposed as the specific endogenous ligand of the kappa opioid receptor (cf. endorphins): C. Chavkin et al., Science 215, 413 (1982). It has also been suggested that dynorphin1-8 or dynorphin1-9 may be transmitters or modulators at the kappa binding site and dynorphins 1-13 and 1-17 may act at a distance from the release site: A. D. Corbett et al., Nature 299, 79 (1982). A possible regulatory role of dynorphin on morphine and b-endorphin-induced analgesia has been proposed: F. Tulunay et al., J. Pharmacol. Exp. Ther. 219, 296 (1981); E. C. Petrie et al., Peptides 3, 41 (1982). Several non-opiate effects have also been described: J. M. Walker et al., Science 218, 1136 (1982); R. Przewlocki et al., ibid. 219, 71 (1983).
Derivative Type: Dynorphin1-13
Additional Names: 1-13-Dynorphin (pig)
Molecular Formula: C75H126N24O15
Molecular Weight: 1603.95
Percent Composition: C 56.16%, H 7.92%, N 20.96%, O 14.96%
Properties: [a]D23 -62.9° (c = 0.5 in 1% acetic acid).
Optical Rotation: [a]D23 -62.9° (c = 0.5 in 1% acetic acid)
Dyphylline Dypnone Dysidiolide Dystrophin Ebastine

Symbol PDYN
Entrez 5173
HUGO 8820
OMIM 131340
RefSeq NM_024411
UniProt P01213
Other data
Locus Chr. 20 pter-p12.2
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Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin.[1] Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal.[2] Occasionally, prodynorphin is not fully processed, leading to the release of “big dynorphin.” This 32-amino acid molecule consists of both dynorphin A and dynorphin B.[3]

Dynorphin A, dynorphin B, and big dynorphin all contain a high proportion of basic amino acid residues, in particular lysine and arginine (29.4%, 23.1%, and 31.2% basic residues, respectively), as well as many hydrophobic residues (41.2%, 30.8%, and 34.4% hydrophobic residues, respectively).[4] Although dynorphins are found widely distributed in the CNS, they have the highest concentrations in the hypothalamus, medulla, pons, midbrain, and spinal cord.[5] Dynorphins are stored in large (80-120 nm diameter) dense-core vesicles that are considerably larger than vesicles storing neurotransmitters. These large dense-core vesicles differ from small synaptic vesicles in that a more intense and prolonged stimulus is needed to cause the large vesicles to release their contents into the synaptic cleft. Dense-core vesicle storage is characteristic of opioid peptides storage.[6]

The first clues to the functionality of dynorphins came from Goldstein et al.[7] in their work with opioid peptides. The group discovered an endogenous opioid peptide in the porcine pituitary that proved difficult to isolate. By sequencing the first 13 amino acids of the peptide, they created a synthetic version of the peptide with a similar potency to the natural peptide. Goldstein et al.[7] applied the synthetic peptide to the guinea ileum longitudinal muscle and found it to be an extraordinarily potent opioid peptide. The peptide was called dynorphin (from the Greek dynamis=power) to describe its potency.[7]

Dynorphins exert their effects primarily through the κ-opioid receptor (KOR), a G-protein-coupled receptor. Two subtypes of KORs have been identified: K1 and K2.[3] Although KOR is the primary receptor for all dynorphins, the peptides do have some affinity for the μ-opioid receptor (MOR), δ-opioid receptor (DOR),and the N-methyl-D-aspartic acid (NMDA)-type glutamate receptor.[6][8] Different dynorphins show different receptor selectivities and potencies at receptors. Big dynorphin and dynorphin A have the same selectivity for human KOR, but dynorphin A is more selective for KOR over MOR and DOR than is big dynorphin. Big dynorphin is more potent at KORs than is dynorphin A. Both big dynorphin and dynorphin A are more potent and more selective than dynorphin B.[9]