Genomes and Genes
Summary: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.
- Walker B, Koob G. Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology. 2008;33:643-52 pubmed
- Brugos B, Hochhaus G. Metabolism of dynorphin A(1-13). Pharmazie. 2004;59:339-43 pubmed..This article is a general review of the metabolism of dynorphin A(1-13) in human plasma and CSF. ..
- Chavkin C. Dynorphin--still an extraordinarily potent opioid peptide. Mol Pharmacol. 2013;83:729-36 pubmed publisher..This article focuses on his contributions to the discovery of the dynorphins and evidence that members of this family of opioid peptides are endogenous agonists for the kappa opioid ..
- Mittelman Smith M, Williams H, Krajewski Hall S, Lai J, Ciofi P, McMullen N, et al. Arcuate kisspeptin/neurokinin B/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology. 2012;153:2800-12 pubmed publisher..These data provide evidence that arcuate KNDy neurons are essential for tonic gonadotropin secretion, the rise in LH after removal of E(2), and the E(2) modulation of body weight. ..
- Walker B, Zorrilla E, Koob G. Systemic ?-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict Biol. 2011;16:116-9 pubmed publisher..Nor-BNI decreased ethanol self-administration in ethanol-dependent animals, with no effect in nondependent animals. Thus, the ?-opioid/dynorphin system is a viable pharmacotherapeutic target for the treatment of alcoholism...
- Shirayama Y, Ishida H, Iwata M, Hazama G, Kawahara R, Duman R. Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. J Neurochem. 2004;90:1258-68 pubmed..These results indicate that both dynorphin A and dynorphin B contribute to the effects of stress, and suggest that blockade of kappa-opioid receptors may have therapeutic potential for the treatment of depression. ..
- Maeda K, Ohkura S, Uenoyama Y, Wakabayashi Y, Oka Y, Tsukamura H, et al. Neurobiological mechanisms underlying GnRH pulse generation by the hypothalamus. Brain Res. 2010;1364:103-15 pubmed publisher..We then discuss possible neurobiological mechanisms underlying GnRH pulse generation, and conclude by proposing that kisspeptin neurons in the arcuate nucleus are key players in this regard. ..
- Land B, Bruchas M, Lemos J, Xu M, Melief E, Chavkin C. The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci. 2008;28:407-14 pubmed publisher..The convergence of stress-induced aversive inputs on the dynorphin system was unexpected, implicates dynorphin as a key mediator of dysphoria, and emphasizes kappa-receptor antagonists as promising therapeutics. ..
- Marvizon J, Chen W, Murphy N. Enkephalins, dynorphins, and beta-endorphin in the rat dorsal horn: an immunofluorescence colocalization study. J Comp Neurol. 2009;517:51-68 pubmed publisher..These results show that enkephalins and dynorphins are present in different populations of dorsal horn neurons. In addition, dynorphin is present in some C-fibers.
- Yakovleva T, Marinova Z, Kuzmin A, Seidah N, Haroutunian V, Terenius L, et al. Dysregulation of dynorphins in Alzheimer disease. Neurobiol Aging. 2007;28:1700-8 pubmedThe opioid peptides dynorphins may be involved in pathogenesis of Alzheimer disease (AD) by inducing neurodegeneration or cognitive impairment...
- Spano M, Ellgren M, Wang X, Hurd Y. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry. 2007;61:554-63 pubmed
- Darmopil S, Martin A, De Diego I, Ares S, Moratalla R. Genetic inactivation of dopamine D1 but not D2 receptors inhibits L-DOPA-induced dyskinesia and histone activation. Biol Psychiatry. 2009;66:603-13 pubmed publisher..In addition, we demonstrate that H3 phosphoacetylation is blocked by D1 receptor inactivation, suggesting that inhibitors of H3 acetylation and/or phosphorylation may be useful in preventing or reversing dyskinesia. ..
- Li Q, Zubieta J, Kennedy R. Practical aspects of in vivo detection of neuropeptides by microdialysis coupled off-line to capillary LC with multistage MS. Anal Chem. 2009;81:2242-50 pubmed publisher..The improvements over previous approaches using capillary LC-MS(n) make in vivo neuropeptide monitoring more practical and feasible for a variety of neuropeptides. ..
- Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro V, et al. Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci. 2010;30:3124-32 pubmed publisher
- Klintenberg R, Andren P. Altered extracellular striatal in vivo biotransformation of the opioid neuropeptide dynorphin A(1-17) in the unilateral 6-OHDA rat model of Parkinson's disease. J Mass Spectrom. 2005;40:261-70 pubmed..The results imply that the extracellular in vivo processing of the dynorphin system is being disturbed in the 6-OHDA-lesion animal model of Parkinson's disease. ..
- Lehman M, Coolen L, Goodman R. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology. 2010;151:3479-89 pubmed publisher..Taken together, this evidence suggests a key role for the KNDy subpopulation as a focal point in the control of reproductive function in health and disease. ..
- Bortolato M, Solbrig M. The price of seizure control: dynorphins in interictal and postictal psychosis. Psychiatry Res. 2007;151:139-43 pubmed..In view of this background, here we introduce the hypothesis that epilepsy-related psychoses may partially result from excessive hippocampal dynorphin release and kappa opioid receptor overstimulation aimed at seizure control. ..
- Shippenberg T, Zapata A, Chefer V. Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther. 2007;116:306-21 pubmed..We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/KOPr system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction. ..
- Mostari P, Ieda N, Deura C, Minabe S, Yamada S, Uenoyama Y, et al. dynorphin-kappa opioid receptor signaling partly mediates estrogen negative feedback effect on LH pulses in female rats. J Reprod Dev. 2013;59:266-72 pubmed..Taken together, the present result suggests that Dyn-KOR signaling is a part of estrogen negative feedback action on GnRH/LH pulses by reducing the kisspeptin release in female rats. ..
- Lai J, Luo M, Chen Q, Ma S, Gardell L, Ossipov M, et al. Dynorphin A activates bradykinin receptors to maintain neuropathic pain. Nat Neurosci. 2006;9:1534-40 pubmed..These data reveal a mechanism for endogenous dynorphin to promote pain through its agonist action at bradykinin receptors and suggest new avenues for therapeutic intervention. ..
- Zhu X, Vincler M, Parker R, Eisenach J. Spinal cord dynorphin expression increases, but does not drive microglial prostaglandin production or mechanical hypersensitivity after incisional surgery in rats. Pain. 2006;125:43-52 pubmed..Although prodynorphin immunoreactivity also increases, it likely does not drive COX-1 expression or mechanical hypersensitivity in this setting. ..
- Navarro V, Gottsch M, Chavkin C, Okamura H, Clifton D, Steiner R. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29:11859-66 pubmed publisher..We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence. ..
- Rance N, Krajewski S, Smith M, Cholanian M, Dacks P. Neurokinin B and the hypothalamic regulation of reproduction. Brain Res. 2010;1364:116-28 pubmed publisher..Future studies will be needed to determine whether NKB signaling plays a permissive role in the onset of puberty or is part of the driving force initiating the maturation of reproductive function. ..
- Goodman R, Coolen L, Anderson G, Hardy S, Valent M, Connors J, et al. Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep. Endocrinology. 2004;145:2959-67 pubmed
- Schwarzer C. 30 years of dynorphins--new insights on their functions in neuropsychiatric diseases. Pharmacol Ther. 2009;123:353-70 pubmed publisherSince the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain...
- Kinsey Jones J, Grachev P, Li X, Lin Y, Milligan S, Lightman S, et al. The inhibitory effects of neurokinin B on GnRH pulse generator frequency in the female rat. Endocrinology. 2012;153:307-15 pubmed publisher..These data show that NKB suppresses the frequency of the GnRH pulse generator in a Dyn/? opioid receptor-dependent fashion. ..
- Bilkei Gorzo A, Erk S, Schürmann B, Mauer D, Michel K, Boecker H, et al. Dynorphins regulate fear memory: from mice to men. J Neurosci. 2012;32:9335-43 pubmed publisher..Here with a translational approach we investigated the role of dynorphins in the formation and extinction of fear memories in mice and in humans...
- Gago B, Fuxe K, Brene S, Diaz Cabiale Z, Reina Sánchez M, Suárez Boomgaard D, et al. Early modulation by the dopamine D4 receptor of morphine-induced changes in the opioid peptide systems in the rat caudate putamen. J Neurosci Res. 2013;91:1533-40 pubmed publisher..The current results present evidence of functional D4 -? opioid receptor interactions, with consequences for the opioid peptide mRNA levels in the rat CPu, contributing to the integration of DA and opioid peptide signaling. ..
- McDermott C, Schrader L. Activation of ? opioid receptors increases intrinsic excitability of dentate gyrus granule cells. J Physiol. 2011;589:3517-32 pubmed publisher..2 subunit protein at the cell surface. These results are consistent with an increase in cell excitability in response to KOR activation and may reflect new possibilities for additional opioid functions. ..
- Goodman R, Lehman M, Smith J, Coolen L, de Oliveira C, Jafarzadehshirazi M, et al. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology. 2007;148:5752-60 pubmed..Because virtually all of these neurons express estrogen and progesterone re-ceptors, they are likely to relay the feedback effects of these steroids to GnRH neurons to regulate reproductive function. ..
- Marinova Z, Vukojevic V, Surcheva S, Yakovleva T, Cebers G, Pasikova N, et al. Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission. J Biol Chem. 2005;280:26360-70 pubmed..We demonstrate that dynorphin A and big dynorphin, consisting of dynorphins A and B, can penetrate into neurons and non-neuronal cells using confocal fluorescence microscopy/immunolabeling...
- Tan No K, Takahashi H, Nakagawasai O, Niijima F, Sato T, Satoh S, et al. Pronociceptive role of dynorphins in uninjured animals: N-ethylmaleimide-induced nociceptive behavior mediated through inhibition of dynorphin degradation. Pain. 2005;113:301-9 pubmed..We have recently reported that dynorphin A and, more potently big dynorphin, consisting of dynorphins A and B, produce the same type of nociceptive response whereas dynorphin B does not [Tan-No K, Esashi A, ..
- Gustafsson L, Zhou Q, Nylander I. Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors. Neuroscience. 2007;146:1137-49 pubmed..The altered sensitivity of the opioid peptides to ethanol may contribute to the previously reported differences in ethanol intake between MS15 and MS360 rats. ..
- Lind J, Gräslund A, Mäler L. Membrane interactions of dynorphins. Biochemistry. 2006;45:15931-40 pubmedThe dynorphins are primarily endogenous ligands to the kappa-opioid receptor, but a variety of non-opioid effects have also been observed, including direct effects on membranes...
- Tamim M, Samadi P, Morissette M, Gregoire L, Ouattara B, Levesque D, et al. Effect of non-dopaminergic drug treatment on Levodopa induced dyskinesias in MPTP monkeys: common implication of striatal neuropeptides. Neuropharmacology. 2010;58:286-96 pubmed publisher..These results show that drugs displaying a wide range of pharmacological activities can modulate L-DOPA induced dyskinesias and this activity is correlated with striatal PPD and PPE mRNA levels suggesting a convergent mechanism...
- Yamamoto N, Soghomonian J. Metabotropic glutamate mGluR5 receptor blockade opposes abnormal involuntary movements and the increases in glutamic acid decarboxylase mRNA levels induced by l-DOPA in striatal neurons of 6-hydroxydopamine-lesioned rats. Neuroscience. 2009;163:1171-80 pubmed publisher..The results also confirm the potential usefulness of antagonists of mGluR5 receptors as adjuncts in the treatment of l-DOPA-induced dyskinesia in patients with Parkinson's disease...
- Block M, Li G, Qin L, Wu X, Pei Z, Wang T, et al. Potent regulation of microglia-derived oxidative stress and dopaminergic neuron survival: substance P vs. dynorphin. FASEB J. 2006;20:251-8 pubmed..Here we demonstrate a tightly regulated mechanism governing microglia-derived oxidative stress, where the neuropeptide balance of dynorphin and substance P is critical to DA neuron survival. ..
- Nguyen X, Masse J, Kumar A, Vijitruth R, Kulik C, Liu M, et al. Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance. Behav Brain Res. 2005;161:254-62 pubmedb>Dynorphins, endogenous kappa-opioid agonists widely expressed in the central nervous system, have been reported to increase following diverse pathophysiological processes, including excitotoxicity, chronic inflammation, and traumatic ..
- Carey A, Borozny K, Aldrich J, McLaughlin J. Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn. Eur J Pharmacol. 2007;569:84-9 pubmed..These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse. ..
- Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren Bemelmans C, Bazov I, et al. Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet. 2010;87:593-603 pubmed publisher..PDYN is the precursor protein for the opioid neuropeptides, ?-neoendorphin, and dynorphins A and B (Dyn A and B)...
- Sardella T, PolgÃ¡r E, Garzillo F, Furuta T, Kaneko T, Watanabe M, et al. Dynorphin is expressed primarily by GABAergic neurons that contain galanin in the rat dorsal horn. Mol Pain. 2011;7:76 pubmed publisher..Since the proportion of GABAergic boutons that contain PPD in these laminae was considerably lower than this, our findings suggest that these neurons may generate relatively small axonal arborisations. ..
- Wee S, Koob G. The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology (Berl). 2010;210:121-35 pubmed publisher..Evidence suggests that abused drugs activate the kappa opioid system, which may play a key role in motivational aspects of dependence. Kappa opioid systems may have an important role in driving compulsive drug intake. ..
- Stanley B, Sher L, Wilson S, Ekman R, Huang Y, Mann J. Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters. J Affect Disord. 2010;124:134-40 pubmed publisher..Based on our findings, we propose a model of non-suicidal self-injury. Our results suggest that drugs acting on the opioid system warrant exploration as pharmacological treatments for NSSI. ..
- Voorn P, van de Witte S, Li K, Jonker A. Dynorphin displaces binding at the glycine site of the NMDA receptor in the rat striatum. Neurosci Lett. 2007;415:55-8 pubmed..This may contribute to the long-term changes in behavioral responsiveness seen after dopamine depletion and treatment with dopaminomimetics which are associated with substantial changes in striatal dynorphin metabolism. ..
- Lindholm S, Ploj K, Franck J, Nylander I. Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain. Alcohol. 2000;22:165-71 pubmed..The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward. ..
- Carta A, Fenu S, Morelli M. Alterations in GAD67, dynorphin and enkephalin mRNA in striatal output neurons following priming in the 6-OHDA model of Parkinson's disease. Neurol Sci. 2001;22:59-60 pubmed..These changes are in relation to the different types of dopamine agonists utilized and suggest that modifications in gene expression induced by priming might be predictive of the dyskinetic potential of a drug. ..
- Sharifi N, Diehl N, Yaswen L, Brennan M, Hochgeschwender U. Generation of dynorphin knockout mice. Brain Res Mol Brain Res. 2001;86:70-5 pubmed..Dynorphin knockout mice constitute a valuable tool for many research areas, among them research into pain, substance abuse, and epilepsy. ..
- Ouyang A, Vos P, Cohen S. Sites of action of mu-, kappa- and sigma-opiate receptor agonists at the feline ileocecal sphincter. Am J Physiol. 1988;254:G224-31 pubmed..mu-Receptor activation causes ICS contraction via a cholinergic pathway. ..
- Reed B, Zhang Y, Chait B, Kreek M. Dynorphin A(1-17) biotransformation in striatum of freely moving rats using microdialysis and matrix-assisted laser desorption/ionization mass spectrometry. J Neurochem. 2003;86:815-23 pubmed..Additional modifications, of mass 42 and 113 Da, were also found on the N-terminus (Ile8 or Pro10) of these same C-terminal fragments. The role of these modifications of C-terminal fragments has not yet been characterized. ..
- Liu B, Qin L, Yang S, Wilson B, Liu Y, Hong J. Femtomolar concentrations of dynorphins protect rat mesencephalic dopaminergic neurons against inflammatory damage. J Pharmacol Exp Ther. 2001;298:1133-41 pubmed..b>Dynorphins are among the major opioid peptides in the striato-nigral pathway and are important in regulating dopaminergic ..
- Tordjman S, Carlier M, Cohen D, Cesselin F, Bourgoin S, Colas Linhart N, et al. Aggression and the three opioid families (endorphins, enkephalins, and dynorphins) in mice. Behav Genet. 2003;33:529-36 pubmed..the possible genetic relationship between intermale aggression and brain levels of enkephalins, endorphins, and dynorphins in 11 inbred strains of mice...
- Sandin J, Tan No K, Kasakov L, Nylander I, Winter A, Silberring J, et al. Differential metabolism of dynorphins in substantia nigra, striatum, and hippocampus. Peptides. 1997;18:949-56 pubmedTo map the proteolytic enzymes metabolizing dynorphins in brain structures, size-exclusion chromatography linked to electrospray ionization mass spectrometry was used...
- Janecka A, Fichna J, Janecki T. Opioid receptors and their ligands. Curr Top Med Chem. 2004;4:1-17 pubmed..Chemical modifications that led to obtaining potent and selective agonists and antagonists for these receptors are discussed. ..
- Ploj K, Roman E, Nylander I. Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats. Neuropeptides. 2003;37:149-56 pubmed..Together, these findings show that repeated periods of MS early in life in male Wistar rats affect the development of the ultrasonic call response and induce long-lasting and possibly permanent alterations in the opioid peptide systems. ..
- Todtenkopf M, Marcus J, Portoghese P, Carlezon W. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology (Berl). 2004;172:463-70 pubmed..These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own. ..
- Terman G, Drake C, Simmons M, Milner T, Chavkin C. Opioid modulation of recurrent excitation in the hippocampal dentate gyrus. J Neurosci. 2000;20:4379-88 pubmed..Thus, kappa opioids can inhibit granule cell recurrent excitation, likely via effects on excitatory mossy fiber collaterals. Such collaterals are thought to be important in mediating temporal lobe epilepsy. ..
- Nylander I, Stenfors C, Tan No K, Mathe A, Terenius L. A comparison between microwave irradiation and decapitation: basal levels of dynorphin and enkephalin and the effect of chronic morphine treatment on dynorphin peptides. Neuropeptides. 1997;31:357-65 pubmed