Retention of heroin and morphine-6β-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1

Alwin G.P. Schuller, Michael A. King, Jiwen Zhang, Elizabeth Bolan, Ying Xian Pan, Daniel J. Morgan, Albert Chang, Maureen E. Czick, Ellen M. Unterwald, Gavril W. Pasternak, John E. Pintar

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Abstract

Morphine produces analgesia by activating mu opioid receptors encoded by the MOR-1 gene. Although morphine-6β-glucuronide (M6G), heroin and 6- acetylmorphine also are considered mu opioids, recent evidence suggests that they act through a distinct receptor mechanism. We examined this question in knockout mice containing disruptions of either the first or second coding exon of MOR-1. Mice homozygous for either MOR-1 mutation were insensitive to morphine. Heroin, 6-acetylmorphine and M6G still elicited analgesia in the exon-1 MOR-1 mutant, which also showed specific M6G binding, whereas M6G and 6-acetylmorphine were inactive in the exon-2 MOR-1 mutant. These results provide genetic evidence for a unique receptor site for M6G and heroin analgesia.

Original languageEnglish (US)
Pages (from-to)151-156
Number of pages6
JournalNature Neuroscience
Volume2
Issue number2
DOIs
StatePublished - Feb 1 1999

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Schuller, A. G. P., King, M. A., Zhang, J., Bolan, E., Pan, Y. X., Morgan, D. J., Chang, A., Czick, M. E., Unterwald, E. M., Pasternak, G. W., & Pintar, J. E. (1999). Retention of heroin and morphine-6β-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1. Nature Neuroscience, 2(2), 151-156. https://doi.org/10.1038/5706