Global InformationDynorphin information
| prodynorphin | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | PDYN | ||||||
| NCBI gene | 5173 | ||||||
| HGNC | 8820 | ||||||
| OMIM | 131340 | ||||||
| RefSeq | NM_024411 | ||||||
| UniProt | P01213 | ||||||
| Other data | |||||||
| Locus | Chr. 20 pter-p12.2 | ||||||
| |||||||
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-neoendorphin.[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". "Big dynorphin" is a 32-amino acid molecule consisting 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, meaning 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]
- ^ Day R, Lazure C, Basak A, Boudreault A, Limperis P, Dong W, Lindberg I (January 1998). "Prodynorphin processing by proprotein convertase 2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity". Journal of Biological Chemistry. 273 (2): 829–836. doi:10.1074/jbc.273.2.829. PMID 9422738.
- ^ Yakovleva T, Bazov I, Cebers G, Marinova Z, Hara Y, Ahmed A, Vlaskovska M, Johansson B, Hochgeschwender U, Singh IN, Bruce-Keller AJ, Hurd YL, Kaneko T, Terenius L, Ekström TJ, Hauser KF, Pickel VM, Bakalkin G (October 2006). "Prodynorphin storage and processing in axon terminals and dendrites". The FASEB Journal. 20 (12): 2124–2126. doi:10.1096/fj.06-6174fje. PMID 16966485. S2CID 2219587.
- ^ a b Nyberg F, Hallberg M (2007). "Neuropeptides in hyperthermia". Neurobiology of Hyperthermia. Progress in Brain Research. Vol. 162. pp. 277–293. doi:10.1016/S0079-6123(06)62014-1. ISBN 978-0-444-51926-9. PMID 17645924.
{{cite book}}:|journal=ignored (help) - ^ Marinova Z, Vukojevic V, Surcheva S, Yakovleva T, Cebers G, Pasikova N, Usynin I, Hugonin L, Fang W, Hallberg M, Hirschberg D, Bergman T, Langel U, Hauser KF, Pramanik A, Aldrich JV, Gräslund A, Terenius L, Bakalkin G (July 2005). "Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission". J. Biol. Chem. 280 (28): 26360–26370. doi:10.1074/jbc.M412494200. PMID 15894804.
- ^ Goldstein A, Ghazarossian VE (October 1980). "Immunoreactive dynorphin in pituitary and brain". Proceedings of the National Academy of Sciences U.S.A. 77 (10): 6207–6710. Bibcode:1980PNAS...77.6207G. doi:10.1073/pnas.77.10.6207. PMC 350244. PMID 6108564.
- ^ a b Drake CT, Chavkin C, Milner TA (2007). "Opioid systems in the dentate gyrus". The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications. Progress in Brain Research. Vol. 163. pp. 245–263. doi:10.1016/S0079-6123(07)63015-5. ISBN 978-0-444-53015-8. PMID 17765723.
{{cite book}}:|journal=ignored (help) - ^ a b c Goldstein A, Tachibana S, Lowney LI, Hunkapiller M, Hood L (December 1979). "Dynorphin-(1-13), an extraordinarily potent opioid peptide". Proceedings of the National Academy of Sciences U.S.A. 76 (12): 6666–6670. Bibcode:1979PNAS...76.6666G. doi:10.1073/pnas.76.12.6666. PMC 411929. PMID 230519.
- ^ Lai J, Luo MC, Chen Q, Ma S, Gardell LR, Ossipov MH, Porreca F (December 2006). "Dynorphin A activates bradykinin receptors to maintain neuropathic pain". Nature Neuroscience. 9 (12): 1534–1540. doi:10.1038/nn1804. PMID 17115041. S2CID 1867322.
- ^ Merg F, Filliol D, Usynin I, Bazov I, Bark N, Hurd YL, Yakovleva T, Kieffer BL, Bakalkin G (April 2006). "Big dynorphin as a putative endogenous ligand for the kappa-opioid receptor". Journal of Neurochemistry. 97 (1): 292–301. doi:10.1111/j.1471-4159.2006.03732.x. PMID 16515546. S2CID 41599853.