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Gene Review

Pdyn  -  prodynorphin

Mus musculus

Synonyms: Beta-neoendorphin-dynorphin, Dyn, Preprodynorphin, Proenkephalin-B
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Disease relevance of Pdyn


Psychiatry related information on Pdyn

  • Effects of big dynorphin (Big Dyn), a prodynorphin-derived peptide consisting of dynorphin A (Dyn A) and dynorphin B (Dyn B) on memory function, anxiety, and locomotor activity were studied in mice and compared to those of Dyn A and Dyn B [5].
  • In the present study, we tested whether (-)-nicotine and U-50,488H prevent delayed-memory impairment induced by beta-amyloid peptide (25-35), and changes of expression of alpha7-type nicotinic acetylcholine receptor mRNA and prodynorphin mRNA [6].

High impact information on Pdyn


Chemical compound and disease context of Pdyn


Biological context of Pdyn

  • Cocaine administration increases activity at dopamine receptors, increases preprodynorphin (ppDyn) gene expression in the caudate-putamen (CPu), and activates the stress responsive hypothalamic-pituitary-adrenal (HPA) axis [12].
  • A recombinant plasmid containing the rat prodynorphin cDNA was introduced into the mouse anterior pituitary corticotroph cell line AtT-20 [13].
  • The amino acid sequence of murine prodynorphin is identical to the rat protein in sequences comprising the opioid peptides and 86% identical in the remainder of the molecule [14].
  • Data regarding the effects of U-69593 and nor-binaltorphimine in KO suggest that the kappa opioid receptor is up-regulated as a consequence of prodynorphin gene deletion and that this adaptation underlies the decrease in basal DA dynamics and cocaine-evoked DA levels observed in DYN KO mice [15].
  • To determine whether absence of dynorphin confers any beneficial effect on spatial learning and memory, knockout mice lacking the coding exons of the gene encoding its precursor prodynorphin (Pdyn) were tested in a water maze task [16].

Anatomical context of Pdyn

  • In this study, we have used in situ hybridization to identify expression sites of mRNAs encoding the delta (delta), kappa (kappa), and mu ( micro) opioid receptors as well as the endogenous opioid peptide precursors proenkephalin (PENK), prodynorphin (PDYN), and proopiomelanocortin (POMC) in pregnant mouse uterus and placenta [17].
  • However, the induction of PPD mRNA in both the dorsal and ventral striatum of mGluR1 minus sign/minus sign mice was significantly less than that of wild-type +/+ mice in response to the two higher doses of SKF-82958 [18].
  • Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20 [13].
  • Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens [15].
  • In dehydrated mice, prodynorphin mRNA was significantly increased in the hypothalamus and nearly all other brain areas examined [19].

Associations of Pdyn with chemical compounds

  • These results support a specific role for MORs in acute cocaine effects on striatal ppEnk gene expression and fail to support critical roles for these receptors in acute cocaine's effects on either ppDyn gene expression or HPA activation [12].
  • The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the straitum of MPTP-treated mice [20].
  • Prodynorphin RNA expression increased within 1 h of glucose stimulation, achieved maximal levels by 4 h, and remained elevated for at least 24 h [14].
  • In ethanol-fed mice, prodynorphin mRNA was also significantly increased in hypothalamus (50-60%) and in most brain areas [19].
  • These results indicate that hypothalamic vasopressin and prodynorphin mRNA can be differentially regulated in certain situations [19].

Regulatory relationships of Pdyn

  • The release of prodynorphin-derived peptides paralleled secretion of endogenous proopiomelanocortin-derived peptides when stimulated by CRF, a natural secretagogue for ACTH [13].

Other interactions of Pdyn

  • Impaired preprodynorphin, but not preproenkephalin, mRNA induction in the striatum of mGluR1 mutant mice in response to acute administration of the full dopamine D(1) agonist SKF-82958 [18].
  • Soon after implantation, all three opioid receptor genes as well as POMC and PENK, but not PDYN, were detected in the uterine environment [17].
  • These results indicate that mGluR1 selectively participates in striatonigral PPD induction in response to D(1) receptor stimulation [18].
  • Previous studies have demonstrated that repeated forced-swim stress-induced behaviors (including analgesia, immobility, and increased drug reward) were mediated by the release of endogenous prodynorphin-derived opioid peptides and subsequent activation of the kappa opioid receptor (KOR) [21].
  • In the LC, numerous genes display common regulation between mouse and rat, including tyrosine hydroxylase, prodynorphin, and galanin [22].

Analytical, diagnostic and therapeutic context of Pdyn

  • Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney [23].
  • Using real-time quantitative PCR, we found that expression of the mu opioid receptor, delta opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in the brain by [Dmt(1)]DALDA treatment [24].
  • Quantitative and conventional microdialysis were used to investigate the effects of constitutive deletion of the prodynorphin gene on basal dopamine (DA) dynamics in the nucleus accumbens (NAc) and the responsiveness of DA neurons to an acute cocaine challenge [15].
  • By Northern blot analysis, the screening of 23 cell lines of endocrine (n = 10) and of nonendocrine (n = 13) origin revealed the presence of high levels of the 2.6-kilobase pro-Dyn transcript only in beta TC3 cells [3].
  • To test this, intact and partially processed proenkephalin and prodynorphin-derived peptides were assessed in OLs using immunocytochemistry or Western blot analysis, or both [25].


  1. Morphine-induced changes in the activity of proopiomelanocortin and prodynorphin systems in zymosan-induced peritonitis in mice. Chadzinska, M., Starowicz, K., Scislowska-Czarnecka, A., Bilecki, W., Pierzchala-Koziec, K., Przewlocki, R., Przewlocka, B., Plytycz, B. Immunol. Lett. (2005) [Pubmed]
  2. A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Lundblad, M., Picconi, B., Lindgren, H., Cenci, M.A. Neurobiol. Dis. (2004) [Pubmed]
  3. Mouse insulinoma beta TC3 cells express prodynorphin messenger ribonucleic acid and derived peptides: a unique cellular model for the study of prodynorphin biosynthesis and processing. Vieau, D., Seidah, N.G., Day, R. Endocrinology (1995) [Pubmed]
  4. Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain. Gardell, L.R., Ibrahim, M., Wang, R., Wang, Z., Ossipov, M.H., Malan, T.P., Porreca, F., Lai, J. Neuroscience (2004) [Pubmed]
  5. Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated effects on memory, anxiolytic-like and locomotor behavior in mice. Kuzmin, A., Madjid, N., Terenius, L., Ogren, S.O., Bakalkin, G. Neuropsychopharmacology (2006) [Pubmed]
  6. Alpha 7-type nicotinic acetylcholine receptor and prodynorphin mRNA expression after administration of (-)-nicotine and U-50,488H in beta-amyloid peptide (25-35)-treated mice. Hiramatsu, M., Watanabe, M., Baba, S., Kojima, R., Nabeshima, T. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  7. DREAM is a critical transcriptional repressor for pain modulation. Cheng, H.Y., Pitcher, G.M., Laviolette, S.R., Whishaw, I.Q., Tong, K.I., Kockeritz, L.K., Wada, T., Joza, N.A., Crackower, M., Goncalves, J., Sarosi, I., Woodgett, J.R., Oliveira-dos-Santos, A.J., Ikura, M., van der Kooy, D., Salter, M.W., Penninger, J.M. Cell (2002) [Pubmed]
  8. Gene expression profiling of facilitated L-LTP in VP16-CREB mice reveals that BDNF is critical for the maintenance of LTP and its synaptic capture. Barco, A., Patterson, S., Alarcon, J.M., Gromova, P., Mata-Roig, M., Morozov, A., Kandel, E.R. Neuron (2005) [Pubmed]
  9. Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells. Ventura, C., Maioli, M. Circ. Res. (2000) [Pubmed]
  10. Mg2+ and Ca2+ differentially regulate DNA binding and dimerization of DREAM. Osawa, M., Dace, A., Tong, K.I., Valiveti, A., Ikura, M., Ames, J.B. J. Biol. Chem. (2005) [Pubmed]
  11. Augmented motor activity and reduced striatal preprodynorphin mRNA induction in response to acute amphetamine administration in metabotropic glutamate receptor 1 knockout mice. Mao, L., Conquet, F., Wang, J.Q. Neuroscience (2001) [Pubmed]
  12. Effects of acute "binge" cocaine on preprodynorphin, preproenkephalin, proopiomelanocortin, and corticotropin-releasing hormone receptor mRNA levels in the striatum and hypothalamic-pituitary-adrenal axis of mu-opioid receptor knockout mice. Zhou, Y., Spangler, R., Schlussman, S.D., Yuferov, V.P., Sora, I., Ho, A., Uhl, G.R., Kreek, M.J. Synapse (2002) [Pubmed]
  13. Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20. Devi, L., Gupta, P., Douglass, J. Mol. Endocrinol. (1989) [Pubmed]
  14. Glucose stimulation of pancreatic beta-cell lines induces expression and secretion of dynorphin. Josefsen, K., Buschard, K., Sørensen, L.R., Wøllike, M., Ekman, R., Birkenbach, M. Endocrinology (1998) [Pubmed]
  15. Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. Chefer, V.I., Shippenberg, T.S. Eur. J. Neurosci. (2006) [Pubmed]
  16. Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance. Nguyen, X.V., Masse, J., Kumar, A., Vijitruth, R., Kulik, C., Liu, M., Choi, D.Y., Foster, T.C., Usynin, I., Bakalkin, G., Bing, G. Behav. Brain Res. (2005) [Pubmed]
  17. Expression of opioid receptors and ligands in pregnant mouse uterus and placenta. Zhu, Y., Pintar, J.E. Biol. Reprod. (1998) [Pubmed]
  18. Impaired preprodynorphin, but not preproenkephalin, mRNA induction in the striatum of mGluR1 mutant mice in response to acute administration of the full dopamine D(1) agonist SKF-82958. Mao, L., Conquet, F., Wang, J.Q. Synapse (2002) [Pubmed]
  19. Prodynorphin and vasopressin mRNA levels are differentially affected by chronic ethanol ingestion in the mouse. Gulya, K., Orpana, A.K., Sikela, J.M., Hoffman, P.L. Brain Res. Mol. Brain Res. (1993) [Pubmed]
  20. The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the straitum of MPTP-treated mice. Ziolkowska, B., Horn, G., Kupsch, A., Höllt, V. Journal of neural transmission. Parkinson's disease and dementia section. (1995) [Pubmed]
  21. Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system. McLaughlin, J.P., Li, S., Valdez, J., Chavkin, T.A., Chavkin, C. Neuropsychopharmacology (2006) [Pubmed]
  22. Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area. McClung, C.A., Nestler, E.J., Zachariou, V. J. Neurosci. (2005) [Pubmed]
  23. Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene. Sharifi, N., Ament, M., Brennan, M.B., Hochgeschwender, U. Neuropeptides (1999) [Pubmed]
  24. Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment. Ben, Y., Smith, A.P., Schiller, P.W., Lee, N.M. Br. J. Pharmacol. (2004) [Pubmed]
  25. Endogenous opioids and oligodendroglial function: possible autocrine/paracrine effects on cell survival and development. Knapp, P.E., Itkis, O.S., Zhang, L., Spruce, B.A., Bakalkin, G., Hauser, K.F. Glia (2001) [Pubmed]
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