Genomes and Genes
Summary: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.
- Kung J, Chen T, Shyu B, Hsiao S, Huang A. Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci. 2010;17:29 pubmed publisherThe present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD)...
- Nagy P, Kettle A, Winterbourn C. Neutrophil-mediated oxidation of enkephalins via myeloperoxidase-dependent addition of superoxide. Free Radic Biol Med. 2010;49:792-9 pubmed publisher..The biochemical interactions of enkephalins with neutrophil-derived oxidants are not well understood...
- DiNieri J, Wang X, Szutorisz H, Spano S, Kaur J, CASACCIA P, et al. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011;70:763-9 pubmed publisher..Prenatal cannabis exposure has been linked to addiction vulnerability, but the neurobiology underlying this risk is unknown...
- Li Y, Lefever M, Muthu D, Bidlack J, Bilsky E, Polt R. Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins. Future Med Chem. 2012;4:205-26 pubmed publisher..Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates. ..
- Loacker S, Sayyah M, Wittmann W, Herzog H, Schwarzer C. Endogenous dynorphin in epileptogenesis and epilepsy: anticonvulsant net effect via kappa opioid receptors. Brain. 2007;130:1017-28 pubmed
- Huang J, Chen J, Wang W, Wang W, Koshimizu Y, Wei Y, et al. Neurochemical properties of enkephalinergic neurons in lumbar spinal dorsal horn revealed by preproenkephalin-green fluorescent protein transgenic mice. J Neurochem. 2010;113:1555-64 pubmed publisher..8 +/- 2.2% and 11.1 +/- 1.6%, respectively. Compared with previously findings obtained with ENK antibody labeling, this line of newly generated mice can be a reliable tool for the study of specific spinal ENKergic neuronal population. ..
- 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...
- Lu Y, McNearney T, Lin W, Wilson S, Yeomans D, Westlund K. Treatment of inflamed pancreas with enkephalin encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae. Mol Ther. 2007;15:1812-9 pubmed..Targeted transgene delivery and met-ENK expression successfully produced decreased inflammation in experimental pancreatitis. ..
- McTavish N, Copeland L, Saville M, Perkins N, Spruce B. Proenkephalin assists stress-activated apoptosis through transcriptional repression of NF-kappaB- and p53-regulated gene targets. Cell Death Differ. 2007;14:1700-10 pubmed
- Cabañero D, Celerier E, Garcia Nogales P, Mata M, Roques B, Maldonado R, et al. The pro-nociceptive effects of remifentanil or surgical injury in mice are associated with a decrease in delta-opioid receptor mRNA levels: Prevention of the nociceptive response by on-site delivery of enkephalins. Pain. 2009;141:88-96 pubmed publisher..The study suggests that down-regulation of DOR contributes to remifentanil and surgery-induced nociception, and that postoperative pain is completely reversed by increasing enkephalin levels in the spinal cord and the periphery. ..
- Noble F, Benturquia N, Bilkei Gorzo A, Zimmer A, Roques B. Use of preproenkephalin knockout mice and selective inhibitors of enkephalinases to investigate the role of enkephalins in various behaviours. Psychopharmacology (Berl). 2008;196:327-35 pubmedThe most simple and efficient method to study the physiological role of enkephalins is to increase the lifetime of these endogenous opioid peptides by inhibiting their inactivating enzymes...
- Kosson D, Klinowiecka A, Kosson P, Bonney I, Carr D, Mayzner Zawadzka E, et al. Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin. Eur J Pain. 2008;12:611-6 pubmed..These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered. ..
- Tajima K, Fukuda T. Region-specific diversity of striosomes in the mouse striatum revealed by the differential immunoreactivities for mu-opioid receptor, substance P, and enkephalin. Neuroscience. 2013;241:215-28 pubmed publisher..The results further suggest the necessity of viewing the striosomes as non-uniform compartments in addition to the traditional dichotomous view, which focuses on discrimination between the striosomes and the matrix. ..
- Durieux P, Bearzatto B, Guiducci S, Buch T, Waisman A, Zoli M, et al. D2R striatopallidal neurons inhibit both locomotor and drug reward processes. Nat Neurosci. 2009;12:393-5 pubmed publisher..Thus D(2)R striatopallidal neurons limit both locomotion and, unexpectedly, drug reinforcement. ..
- Tang J, Lipkowski A, Specter S. Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro. Pharmacol Rep. 2008;60:190-8 pubmed..In conclusion, biphalin applied primarily as a new medicine for chronic pain treatment in AIDS patients may play a significant beneficial role as a component of antiviral HIV multidrug therapies. ..
- Chen T, Cheng Y, Sun W, Shyu B. Differential regulation of morphine antinociceptive effects by endogenous enkephalinergic system in the forebrain of mice. Mol Pain. 2008;4:41 pubmed publisher..However the functional role of enkephalins in the supraspinal nociceptive processing and their underlying mechanism is not clear...
- Nilsson A, Fälth M, Zhang X, Kultima K, Sköld K, Svenningsson P, et al. Striatal alterations of secretogranin-1, somatostatin, prodynorphin, and cholecystokinin peptides in an experimental mouse model of Parkinson disease. Mol Cell Proteomics. 2009;8:1094-104 pubmed publisher..This study provides further evidence that neuropeptides take part in mediating the central nervous system failure associated with Parkinson disease. ..
- Lazarczyk M, Matyja E, Lipkowski A. A comparative study of morphine stimulation and biphalin inhibition of human glioblastoma T98G cell proliferation in vitro. Peptides. 2010;31:1606-12 pubmed publisher..Our experiments have shown that biphalin might constitute an alternative solution for morphine application in anti-pain and anti-cancer therapy. ..
- 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. ..
- Pavon N, Martin A, Mendialdua A, Moratalla R. ERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry. 2006;59:64-74 pubmed..We have developed a model of L-DOPA-induced dyskinesias in mice that reproduces the main clinical features of dyskinesia in humans...
- 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
- Bezard E, Gross C, Brotchie J. Presymptomatic compensation in Parkinson's disease is not dopamine-mediated. Trends Neurosci. 2003;26:215-21 pubmed
- Clarke S, Zimmer A, Zimmer A, Hill R, Kitchen I. Region selective up-regulation of micro-, delta- and kappa-opioid receptors but not opioid receptor-like 1 receptors in the brains of enkephalin and dynorphin knockout mice. Neuroscience. 2003;122:479-89 pubmed..Prodynorphin peptides appear to regulate mostly the kappa-receptor but they are also modulators of micro- and delta-receptors. ..
- McLaughlin J, Marton Popovici M, Chavkin C. Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J Neurosci. 2003;23:5674-83 pubmed..The findings suggest that chronic swim stress may activate the kappa opioid system to produce analgesia, immobility, and potentiation of the acute rewarding properties of cocaine in C57Bl/6 mice. ..
- Will M, Vanderheyden W, Kelley A. Striatal opioid peptide gene expression differentially tracks short-term satiety but does not vary with negative energy balance in a manner opposite to hypothalamic NPY. Am J Physiol Regul Integr Comp Physiol. 2007;292:R217-26 pubmed..This double dissociation between striatal and hypothalamic peptide systems suggests a specific role for striatal PPE in relatively short-term food motivational states, but not in long-term metabolic responses to diet restriction. ..
- Hubert G, Kuhar M. Colocalization of CART peptide with prodynorphin and dopamine D1 receptors in the rat nucleus accumbens. Neuropeptides. 2006;40:409-15 pubmed
- Nitsche J, Schuller A, King M, Zengh M, Pasternak G, Pintar J. Genetic dissociation of opiate tolerance and physical dependence in delta-opioid receptor-1 and preproenkephalin knock-out mice. J Neurosci. 2002;22:10906-13 pubmed
- Metz Boutigue M, Goumon Y, Strub J, Lugardon K, Aunis D. Antimicrobial chromogranins and proenkephalin-A-derived peptides: Antibacterial and antifungal activities of chromogranins and proenkephalin-A-derived peptides. Ann N Y Acad Sci. 2003;992:168-78 pubmed
- Lecoq I, Marie N, Jauzac P, Allouche S. Different regulation of human delta-opioid receptors by SNC-80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and endogenous enkephalins. J Pharmacol Exp Ther. 2004;310:666-77 pubmed..These data strongly suggested a differential sorting of the internalized receptors caused by enkephalins and SNC-80 that was further confirmed by chloroquine as a lysosomal degradation blocker and monensin as a ..
- Ogden C, Rich M, Schork N, Paulus M, Geyer M, Lohr J, et al. Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach. Mol Psychiatry. 2004;9:1007-29 pubmed
- Khalap A, Bagrosky B, Lecaude S, Youson J, Danielson P, Dores R. Trends in the evolution of the proenkephalin and prodynorphin genes in gnathostomes. Ann N Y Acad Sci. 2005;1040:22-37 pubmed..Current studies on the opioid/orphanin gene family point to the duplication events that shaped this family occurring prior to the radiation of the gnathostomes. ..
- Tel B, Zeng B, Cannizzaro C, Pearce R, Rose S, Jenner P. Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets. Neuroscience. 2002;115:1047-58 pubmed
- Berrendero F, Mendizabal V, Robledo P, Galeote L, Bilkei Gorzo A, Zimmer A, et al. Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. J Neurosci. 2005;25:1103-12 pubmed..In the present study, the participation of endogenous enkephalins on nicotine responses has been investigated by using preproenkephalin knock-out mice...
- Sinnaeve B, Storme M, Van Bocxlaer J. Capillary liquid chromatography and tandem mass spectrometry for the quantification of enkephalins in cerebrospinal fluid. J Sep Sci. 2005;28:1779-84 pubmedA capillary LC-MS/MS system was evaluated for the absolute quantification of enkephalins in cerebrospinal fluid (CSF). On column focusing on a C18 trapping column, in-line with the analytical column, was used for preconcentration...
- Vengadesan K, Gautham N. Conformational studies on enkephalins using the MOLS technique. Biopolymers. 2004;74:476-94 pubmed..The study also provides information on the distribution of the low energy conformations that we have classified on the basis of structural motifs, backbone hydrogen-bonding patterns, and root mean square deviations in atomic positions. ..
- Kelley A, Baldo B, Pratt W. A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol. 2005;493:72-85 pubmed
- Aubert I, Guigoni C, Li Q, Dovero S, Bioulac B, Gross C, et al. Enhanced preproenkephalin-B-derived opioid transmission in striatum and subthalamic nucleus converges upon globus pallidus internalis in L-3,4-dihydroxyphenylalanine-induced dyskinesia. Biol Psychiatry. 2007;61:836-44 pubmed
- Hao S, Mata M, Goins W, Glorioso J, Fink D. Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain. Pain. 2003;102:135-42 pubmed..The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically. ..
- Klintenberg R, Svenningsson P, Gunne L, Andren P. Naloxone reduces levodopa-induced dyskinesias and apomorphine-induced rotations in primate models of parkinsonism. J Neural Transm (Vienna). 2002;109:1295-307 pubmed..Taken together the present results suggest a possible role for the endogenous opioid system in the pathogenesis of levodopa-induced dyskinesia in primates. ..
- Nieto M, Guen S, Kieffer B, Roques B, Noble F. Physiological control of emotion-related behaviors by endogenous enkephalins involves essentially the delta opioid receptors. Neuroscience. 2005;135:305-13 pubmedThe endogenous pentapeptide enkephalins bind to the mu and delta opioid receptors, with a slightly higher affinity for the latter...
- Goss J, Harley C, Mata M, O Malley M, Goins W, Hu X, et al. Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann Neurol. 2002;52:662-5 pubmed..These results suggest that gene transfer with an enkephalin-expressing vector may be used to treat pain resulting from cancer in bone. ..
- Lundblad M, Vaudano E, Cenci M. Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l-DOPA-induced dyskinesia. J Neurochem. 2003;84:1398-410 pubmed..Cotreatment with KW-6002 and L-DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug. ..
- Sun Z, Del Mar N, Meade C, Goldowitz D, Reiner A. Differential changes in striatal projection neurons in R6/2 transgenic mice for Huntington's disease. Neurobiol Dis. 2002;11:369-85 pubmed..The selective reduction in striatal PPE in R6/2 mice is reminiscent of adult-onset HD, but the preservation of the striatonigral projection system is not. Thus, R6/2 mice do not strictly mimic adult-onset HD in their striatal pathology. ..
- Yakovleva T, Bazov I, Cebers G, Marinova Z, Hara Y, Ahmed A, et al. Prodynorphin storage and processing in axon terminals and dendrites. FASEB J. 2006;20:2124-6 pubmed..Regulation of PDYN storage and processing at synapses by neuronal activity or extracellular stimuli may provide a local mechanism for regulation of synaptic transmission. ..
- Le Y, Gagneten S, Larson T, Santha E, Dobi A, v Agoston D, et al. Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy. J Neurochem. 2003;84:689-97 pubmed..These results suggest that conservation of the far-upstream DNA elements serves more subtle roles, such as the developmental or cell-specific expression of the ENK gene. ..
- Yeomans D, Lu Y, Laurito C, Peters M, Vota Vellis G, Wilson S, et al. Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia. Mol Ther. 2006;13:589-97 pubmed..This approach may be a viable means of treating localized cutaneous burning pain and hyperalgesia. ..
- Bilkei Gorzo A, Racz I, Michel K, Zimmer A, Klingmuller D, Zimmer A. Behavioral phenotype of pre-proenkephalin-deficient mice on diverse congenic backgrounds. Psychopharmacology (Berl). 2004;176:343-52 pubmed..2) The behavior of the background strain should be considered in the analysis of knockout mice to avoid floor and ceiling effects, which may mask the phenotype. ..
- Reiner A. Can lesions of GPe correct HD deficits?. Exp Neurol. 2004;186:1-5 pubmed
- Glorioso J, Mata M, Fink D. Gene therapy for chronic pain. Curr Opin Mol Ther. 2003;5:483-8 pubmed..A clinical trial is set to commence. ..
- Yeomans D, Jones T, Laurito C, Lu Y, Wilson S. Reversal of ongoing thermal hyperalgesia in mice by a recombinant herpesvirus that encodes human preproenkephalin. Mol Ther. 2004;9:24-9 pubmed..These results suggest that herpesvirus vectors encoding analgesic peptides may be useful in attenuating centrally mediated, ongoing neuropathic pain and/or hyperalgesia. ..
- Skoubis P, Lam H, Shoblock J, Narayanan S, Maidment N. Endogenous enkephalins, not endorphins, modulate basal hedonic state in mice. Eur J Neurosci. 2005;21:1379-84 pubmed..5, 5 and 10 mg/kg s.c.). These data suggest that enkephalins, but not endorphins, may mediate an endogenous opioid component of basal affective state and also indicate that ..
- Hayward M, Pintar J, Low M. Selective reward deficit in mice lacking beta-endorphin and enkephalin. J Neurosci. 2002;22:8251-8 pubmed..Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis. ..
- Marquez P, Baliram R, Gajawada N, Friedman T, Lutfy K. Differential involvement of enkephalins in analgesic tolerance, locomotor sensitization, and conditioned place preference induced by morphine. Behav Neurosci. 2006;120:10-5 pubmedIn this study, the authors investigated the role of enkephalins in morphine-induced conditioned place preference, locomotor sensitization, and analgesic tolerance...
- Fagergren P, Smith H, Daunais J, Nader M, Porrino L, Hurd Y. Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration. Eur J Neurosci. 2003;17:2212-8 pubmed..In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence. ..
- Yasothornsrikul S, Greenbaum D, Medzihradszky K, Toneff T, Bundey R, Miller R, et al. Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Proc Natl Acad Sci U S A. 2003;100:9590-5 pubmed..These findings indicate a previously uncharacterized biological role for secretory vesicle cathepsin L in the production of [Met]enkephalin, an endogenous peptide neurotransmitter. ..
- Henry B, Duty S, Fox S, Crossman A, Brotchie J. Increased striatal pre-proenkephalin B expression is associated with dyskinesia in Parkinson's disease. Exp Neurol. 2003;183:458-68 pubmed..Increased PPE-B mRNA expression, with subsequent elevations in opioid peptide transmission within the direct striatal output pathways, may underlie treatment-related dyskinesia in Parkinson's disease. ..
- Todd A, Hughes D, Polgar E, Nagy G, Mackie M, Ottersen O, et al. The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur J Neurosci. 2003;17:13-27 pubmed..As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter. ..
- Canals J, Pineda J, Torres Peraza J, Bosch M, Martín Ibáñez R, Muñoz M, et al. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci. 2004;24:7727-39 pubmed..Hence, administration of exogenous BDNF may delay or stop illness progression. ..