Reduced expression of a novel mu-opioid receptor (MOR) subtype MOR-1B in CXBK mice: implications of MOR-1B in the expression of MOR-mediated responses

Eur J Neurosci. 2003 Dec;18(12):3193-8. doi: 10.1111/j.1460-9568.2003.03052.x.


A novel mu-opioid receptor (MOR) subtype, named MOR-1B, derived from alternatively spliced variants of MOR gene, has been isolated from the rat brain. Here we found for the first time that CXBK recombinant-inbred mice display a significant reduction in the expression of MOR-1B mRNA in the brain as compared to that in their progenitor C57BL/6 mice. In contrast, the expression level of MOR-1 mRNA in the brain of CXBK mice was similar to that found in C57BL/6 mice. Furthermore, relatively lower levels of MOR-1B immunoreactivity were detected in the periaqueductal grey matter (PAG) of CXBK mice than that observed in C57BL/6 mice. To investigate further the possible changes in MOR function to activate G-proteins under the condition of a reduced MOR-1B expression, the guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding assay was performed. We found that the increased level of [35S]GTPgammaS bindings to whole brain membranes induced by a selective MOR agonist endomorphin-1 was significantly decreased in CXBK mice, indicating that CXBK strain can be classified as MOR-1B-knockdown mice. We next investigated whether intracerebroventricular (i.c.v.) pretreatment with an antisence oligodeoxynucleotide against exon 5 of MOR gene (MOR-1B) could affect the endomorphin-1-induced supraspinal antinociception. The i.c.v. pretreatment with antisence oligodeoxynucleotide against MOR-1B produced a significant reduction in the i.c.v.-administered endomorphin-1-induced antinociceptive effect. The present data provide first evidence that a lack of MOR-1B expression may, at least in part, contribute to the reduced sensitivity to MOR agonists in CXBK mice, and MOR-1B may play a potential role in the MOR-mediated supraspinal antinociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Brain / metabolism*
  • Brain Chemistry / genetics*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Oligonucleotides, Antisense / pharmacology
  • Oligopeptides / pharmacology
  • Pain / drug therapy
  • Pain / genetics
  • Pain / metabolism
  • Protein Isoforms / drug effects
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Radioligand Assay
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism*
  • Sulfur Radioisotopes


  • Oligonucleotides, Antisense
  • Oligopeptides
  • Protein Isoforms
  • Receptors, Opioid, mu
  • Sulfur Radioisotopes
  • endomorphin 1
  • Guanosine 5'-O-(3-Thiotriphosphate)