Involvement of the 3′ non‐coding region of the mu opioid receptor gene in morphine‐induced analgesia

• Published in: Psychiatry and clinical neurosciences Vol. 60; no. s1; pp. S11 - S17
• Main Authors: KASAI, SHINYA, HAN, WENHUA, IDE, SOICHIRO, HATA, HARUMI, TAKAMATSU, YUKIO, YAMAMOTO, HIDEKO, UHL, GEORGE R., SORA, ICHIRO, IKEDA, KAZUTAKA
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.04.2006
• Subjects: 3′ untranslated region; analgesia; CXBK mice; morphine; mu opioid receptor
• ISSN: 1323-1316; 1440-1819
• DOI: 10.1111/j.1440-1819.2006.01523.x-i1

The mu opioid receptor (MOR) is known to play an essential role in morphine‐induced analgesia. MOR‐1 mRNA, the major MOR transcript, possesses a long 3′ untranslated region (3′UTR) in both mouse and human species. The sequence of the MOR‐1 3′UTR, especially that of its 3′ end region, is conserved between mice and humans. In the MOR‐1 3′UTR, AU‐rich elements (AREs) are densely localized at the 3′ end region, suggesting low stability of this mRNA. Numerous putative transcription factor‐binding motifs are located in the 3′ non‐coding regions of the mouse and human MOR genes. The CXBK mouse strain, known as a MOR‐deficient strain, possesses a decreased amount of MOR‐1 mRNA containing an abnormally long MOR‐1 3′UTR with a long nucleotide insertion. This insert might disrupt the stability of the MOR‐1 mRNA or might reduce the transcription of the MOR‐1 mRNA by separating the transcription factor‐binding motifs in the 3′ non‐coding region of the MOR gene, thereby decreasing MOR‐1 mRNA expression and attenuating morphine‐induced analgesia in CXBK mice. These recent findings suggest that the MOR‐1 3′UTR is involved in mRNA expression and in the difference in response to morphine. This possible genetic mechanism may provide a good starting point for designing effective pain treatments with opiates.