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Titolo:
The untranslated region of mu-opioid receptor mRNA contributes to reduced opioid sensitivity in CXBK mice
Autore:
Ikeda, K; Kobayashi, T; Ichikawa, T; Kumanishi, T; Niki, H; Yano, R;
Indirizzi:
RIKEN, Brain Sci Inst, Lab Neurobiol Emot, Wako, Saitama 3510198, Japan RIKEN Wako Saitama Japan 3510198 obiol Emot, Wako, Saitama 3510198, Japan RIKEN, Brain Sci Inst, Lab Cellular Informat Proc, Wako, Saitama 3510198, Japan RIKEN Wako Saitama Japan 3510198 ormat Proc, Wako, Saitama 3510198, Japan Niigata Univ, Brain Res Inst, Dept Mol Neuropathol, Niigata 9518585, JapanNiigata Univ Niigata Japan 9518585 l Neuropathol, Niigata 9518585, Japan
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 4, volume: 21, anno: 2001,
pagine: 1334 - 1339
SICI:
0270-6474(20010215)21:4<1334:TUROMR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL HEMIPLEGIC MIGRAINE; MORPHINE-INDUCED ANALGESIA; INBRED MOUSE STRAINS; MESSENGER-RNA; OPIATE RECEPTOR; FUNCTIONAL COUPLINGS; DEFICIENT MICE; GENE; CHANNEL; LACKING;
Keywords:
CXBK mouse; mu-opioid receptor; UTR; individual difference; analgesia; morphine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Ikeda, K Tokyo Inst Psychiat, Dept Psychopharmacol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan Tokyo Inst Psychiat 2-1-8 Kamikitazawa Tokyo Japan 1568585 Japan
Citazione:
K. Ikeda et al., "The untranslated region of mu-opioid receptor mRNA contributes to reduced opioid sensitivity in CXBK mice", J NEUROSC, 21(4), 2001, pp. 1334-1339

Abstract

It is well known that there are individual differences in a sensitivity toanalgesics. Several lines of evidence have suggested that the level of opioid-induced analgesia is dependent on the level of expression of the mu -opioid receptor (mu -OR). However, the molecular mechanisms underlying the diversity of the level of the opioid receptor and the opioid sensitivity among individuals remain to be elucidated. In the present study, we analyzed the opioid-receptor genes of CXBK recombinant-inbred mice, which show reducedsensitivity to opioids. Northern blotting, nucleotide sequencing, and in situ hybridization histochemical analyses demonstrated that CXBK mice possessed mu -OR mRNA with a normal coding region but an abnormally long untranslated region (UTR). In addition, the mu -OR mRNA level in CXBK mice was lessthan in the control mice. Next, we produced littermate mice that had inherited two copies of the wild-type mu -OR gene, had inherited two copies of the CXBK mu -OR gene, and had inherited both copies of the mu -OR genes. In these mice, inheritance of the CXBK mu -OR gene was well correlated with less mu -OR mRNA and reduced opioid effects on nociception and locomotor activity. We conclude that the CXBK mu -OR gene is responsible for the CXBK phenotypes. Because UTR differences are known to affect the level of the corresponding mRNA and protein and because UTRs are more divergent among individuals than coding regions, the present findings suggest that opioid sensitivity may vary, depending on different mu -OR levels attributable to divergent UTR of mu -OR mRNA.

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Documento generato il 03/04/20 alle ore 04:22:27