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Oprk1  -  opioid receptor, kappa 1

Mus musculus

Synonyms: K-OR-1, KOR, KOR-1, Kappa-type opioid receptor, MSL-1, ...
 
 
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Disease relevance of Oprk1

 

Psychiatry related information on Oprk1

 

High impact information on Oprk1

  • The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids [4].
  • In contrast, U50,488 treatment of AtT-20 cells expressing KOR having alanine substituted for serine-369 (KSA) did not increase phospho-p38 [5].
  • Enhanced binding of Sp1 to this GC box correlates with RA induction of KOR gene [1].
  • The mouse kappa opioid receptor (KOR) gene is constitutively expressed in mouse embryonal carcinoma P19 stem cells and suppressed by retinoic acid (RA) in cells undergoing neuronal differentiation [6].
  • Overexpression of Ik-1 in P19 suppresses endogenous KOR gene expression, accompanied by increased binding of Ik-1 to the Ik-binding site and chromatin histone deacetylation on KOR promoters [6].
 

Chemical compound and disease context of Oprk1

 

Biological context of Oprk1

  • Search of the Celera Genomics database indicated that DBA/2J had several SNP sites in the promoter/regulatory regions, which might explain the different expression of Oprk1 mRNA subtypes in this strain [9].
  • Similarly, improgan analgesia was equivalent in all three genotypes of KOR-1 mutant mice, whereas kappa-mediated analgesia (U50,488) and kappa opioid (3H-U69,593) binding were abolished in the homozygous (-/-) mice [10].
  • The mouse kappa opioid receptor (KOR) gene uses two functional polyadenylation signals, separated by a distance of approximately 2.2 kilobases (kb) in the 3'-end of the gene [11].
  • A negative regulatory pathway for KOR transcription involves a putative enhancer region in its 3'-UTR [11].
  • Utilization of different poly(A) of the KOR gene produces KOR transcripts of different mRNA stability, transcription efficiency, and regulatability [11].
 

Anatomical context of Oprk1

  • At time 0 (controls) and 4 and 24h after stimulation, peritoneal leukocytes (PTLs) were counted, PTL levels of opioid peptides (beta-endorphin and dynorphin) measured by radioimmunoassays, while mRNAs coding their respective precursors (POMC and PDYN) and receptors (MOR and KOR) determined by QRT-PCR [12].
  • Three kappa-opioid receptor (KOR) mRNA isoforms have been detected in different parts of the central nervous system [13].
  • The 5'- and 3'-untranslated regions (UTRs) of KOR, either alone or in combination, are able to mediate transport of mRNAs to processes of P19 neurons and axons of dorsal root ganglia [13].
  • The antiexudative effects of KOR and DOR agonists in animals treated with nitric oxide synthase (NOS) inhibitors and their protein levels in the gut (whole jejunum and mucosa) and spinal cord of mice with chronic intestinal inflammation were also measured [14].
  • Protein levels of KOR and DOR in the whole jejunum and mucosa were significantly increased after chronic inflammation [14].
 

Associations of Oprk1 with chemical compounds

  • Retinoic acid specifically suppresses the expression of KOR transcripts using the second poly(A) in P19 cells [11].
  • The potency of the KOR agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolydinyl)cyclohexyl]-benzeneazetamine (U50,488H) inhibiting plasma extravasation was enhanced 26.3 times during chronic compared with acute inflammation [14].
  • Furthermore, DAMGO ([D-Ala(2),MePhe(4), Gly-ol(5)]-enkephalin), a mu-opioid receptor (MOR) agonist, and U-69593, a kappa-opioid receptor (KOR) agonist, but not DSLET ([D-Ser(2)]Leu-enkephalin-Thr(6)), a delta-opioid receptor agonist, showed similar analgesia on the BK responses [15].
  • Mice deficient in the kappa-opioid receptor (KOR) gene have recently been developed by the technique of homologous recombination and shown to lack behavioural responses to the selective kappa1-receptor agonist U-50,488H [16].
  • Mice lacking the mu-delta-kappa-opioid receptor (MOR/DOR/KOR) genes and their corresponding wild-type littermates have been used to quantify NPFF(1) and NPFF(2) (neuropeptide FF) receptors by in vitro autoradiography in the central nervous tissues [17].
 

Regulatory relationships of Oprk1

  • The increased DA uptake after pharmacological inactivation or gene deletion highlights the plasticity of mesoaccumbal DA neurons and suggests that loss of KOR-1 and the resultant disinhibition of DA neurons trigger short- and long-term DA transporter adaptations that maintain normal DA levels, despite enhanced release [18].
 

Other interactions of Oprk1

  • MOR mRNA was increased 24h after injection in Z and ZM groups, while KOR mRNA was similar in all groups except of decrease in Z at 24h [12].
  • 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) [19].
  • T and B lymphocyte proliferative capabilities in vitro, Natural Killer activity and steady-state Ig levels were unchanged in KOR-/- mice [20].
 

Analytical, diagnostic and therapeutic context of Oprk1

  • To investigate the contribution of the kappa-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting [21].
  • We have carried out quantitative autoradiography of mu-, delta- and kappa1 receptors in the brains of wild-type (+/+), heterozygous (+/-) and homozygous (-/-) KOR knockout mice to determine if there is any compensatory expression of mu- and delta-receptor subtypes in mutant animals [16].
  • Based upon Northern blot analysis, KOR transcript is estimated to be approximately 6 kb in length [22].
  • Microdialysis revealed that basal DA release and DA extraction fraction (Ed), an indirect measure of DA uptake, are enhanced in KOR-1 knock-out mice [18].
  • Here we examined the effects of targeted disruption of kappa-opioid receptor (KOR) on oral alcohol self-administration and other behaviors [3].

References

  1. Induction of the mouse kappa-opioid receptor gene by retinoic acid in P19 cells. Li, J., Park, S.W., Loh, H.H., Wei, L.N. J. Biol. Chem. (2002) [Pubmed]
  2. Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. Xu, M., Petraschka, M., McLaughlin, J.P., Westenbroek, R.E., Caron, M.G., Lefkowitz, R.J., Czyzyk, T.A., Pintar, J.E., Terman, G.W., Chavkin, C. J. Neurosci. (2004) [Pubmed]
  3. Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. Kovacs, K.M., Szakall, I., O'Brien, D., Wang, R., Vinod, K.Y., Saito, M., Simonin, F., Kieffer, B.L., Vadasz, C. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  4. Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Filliol, D., Ghozland, S., Chluba, J., Martin, M., Matthes, H.W., Simonin, F., Befort, K., Gavériaux-Ruff, C., Dierich, A., LeMeur, M., Valverde, O., Maldonado, R., Kieffer, B.L. Nat. Genet. (2000) [Pubmed]
  5. Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. Bruchas, M.R., Macey, T.A., Lowe, J.D., Chavkin, C. J. Biol. Chem. (2006) [Pubmed]
  6. An intronic Ikaros-binding element mediates retinoic acid suppression of the kappa opioid receptor gene, accompanied by histone deacetylation on the promoters. Hu, X., Bi, J., Loh, H.H., Wei, L.N. J. Biol. Chem. (2001) [Pubmed]
  7. Regulation of mouse kappa opioid receptor gene expression by retinoids. Bi, J., Hu, X., Loh, H.H., Wei, L.N. J. Neurosci. (2001) [Pubmed]
  8. A novel signaling pathway of nitric oxide on transcriptional regulation of mouse kappa opioid receptor gene. Park, S.W., Li, J., Loh, H.H., Wei, L.N. J. Neurosci. (2002) [Pubmed]
  9. Variants of kappa-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice. Saito, M., Ehringer, M.A., Toth, R., Oros, M., Szakall, I., Sikela, J.M., Vadasz, C. Alcohol (2003) [Pubmed]
  10. Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice. Hough, L.B., Nalwalk, J.W., Chen, Y., Schuller, A., Zhu, Y., Zhang, J., Menge, W.M., Leurs, R., Timmerman, H., Pintar, J.E. Brain Res. (2000) [Pubmed]
  11. Regulation of mouse kappa opioid receptor gene expression by different 3'-untranslated regions and the effect of retinoic acid. Hu, X., Bi, J., Loh, H.H., Wei, L.N. Mol. Pharmacol. (2002) [Pubmed]
  12. 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]
  13. Mouse kappa-opioid receptor mRNA differential transport in neurons. Bi, J., Hu, X., Loh, H.H., Wei, L.N. Mol. Pharmacol. (2003) [Pubmed]
  14. Antiexudative effects of opioids and expression of kappa- and delta-opioid receptors during intestinal inflammation in mice: involvement of nitric oxide. Jiménez, N., Puig, M.M., Pol, O. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  15. Protein kinase C-mediated acute tolerance to peripheral mu-opioid analgesia in the bradykinin-nociception test in mice. Inoue, M., Ueda, H. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  16. Quantitative autoradiography of mu-,delta- and kappa1 opioid receptors in kappa-opioid receptor knockout mice. Slowe, S.J., Simonin, F., Kieffer, B., Kitchen, I. Brain Res. (1999) [Pubmed]
  17. Opposite alterations of NPFF1 and NPFF2 neuropeptide FF receptor density in the triple MOR/DOR/KOR-opioid receptor knockout mouse brains. Gouardères, C., Kieffer, B.L., Zajac, J.M. J. Chem. Neuroanat. (2004) [Pubmed]
  18. Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine. Chefer, V.I., Czyzyk, T., Bolan, E.A., Moron, J., Pintar, J.E., Shippenberg, T.S. J. Neurosci. (2005) [Pubmed]
  19. 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]
  20. Enhanced humoral response in kappa-opioid receptor knockout mice. Gavériaux-Ruff, C., Simonin, F., Filliol, D., Kieffer, B.L. J. Neuroimmunol. (2003) [Pubmed]
  21. Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal. Simonin, F., Valverde, O., Smadja, C., Slowe, S., Kitchen, I., Dierich, A., Le Meur, M., Roques, B.P., Maldonado, R., Kieffer, B.L. EMBO J. (1998) [Pubmed]
  22. Cloning and promoter mapping of mouse kappa opioid receptor gene. Liu, H.C., Lu, S., Augustin, L.B., Felsheim, R.F., Chen, H.C., Loh, H.H., Wei, L.N. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
 
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