Reduced expression of a novel µ‐opioid receptor (MOR) subtype MOR‐1B in CXBK mice: Implications of MOR‐1B in the expression of MOR‐mediated responses

AbstractA novel µ‐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]GTPγS) binding assay was performed. We found that the increased level of [35S]GTPγS 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.