title: 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.
abstract: 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.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imai
authors.forename: Satoru
authors.initials: S
authors.lastname: Ozaki
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Michiko
authors.initials: M
authors.lastname: Narita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013462:Sulfur Radioisotopes
chemical_list: D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; C105293:endomorphin 1; D016244:Guanosine 5'-O-(3-Thiotriphosphate)