Lack of μ-opioid receptor-mediated G-protein activation in the spinal cord of mice lacking exon 1 or exons 2 and 3 of the MOR-1 gene

Hirokazu Mizoguchi, Hsiang En Wu, Minoru Narita, Ichiro Sora, F. Scott Hall, George R. Uhl, Horace H. Loh, Hiroshi Nagase, Leon F. Tseng

Research output: Contribution to journalArticle

Abstract

The G-protein activation induced by μ-opioid receptor agonists was determined in spinal cord membranes from two types of μ-opioid receptor knockout mice: mice with a disruption of exon 1 (MOR (Exon 1)-KO) or exons 2 and 3 (MOR (Exons 2 and 3)-KO) of the μ-opioid receptor gene. The G-protein activation induced by the opioid agonists was measured by monitoring the increases of guanosine-5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding. The μ-opioid receptor agonists (D-Ala2,N-MePhe4,Gly-ol5]enkephalin, endomorphin-1, endomorphin-2, morphine, morphine-6β-glucuronide, and fentanyl produced concentration-dependent increases of [35S]GTPγS binding to spinal cord membranes in wild-type mice, but not in MOR (Exon 1)-KO mice or MOR (Exons 2 and 3)-KO mice. On the other hand, the δ-opioid receptor agonist [D-Pen2,5]enkephalin, the κ-opioid receptor agonist (-)U50,488H, or the ORL1-receptor agonist nociception increased [35S]GTPγS binding in the spinal cord membranes from both MOR (Exon 1)-KO mice and MOR (Exons 2 and 3)-KO mice to the same extent as in the corresponding wild-type mice. The results provide further information about the important roles of the sequences encoded within exon 1 and exons 2 and 3 of μ-opioid receptor gene for the activation of G-proteins by μ-opioid receptor agonists in the mouse spinal cord.

Original languageEnglish (US)
Pages (from-to)423-429
Number of pages7
JournalJournal of Pharmacological Sciences
Volume93
Issue number4
DOIs
StatePublished - Dec 2003
Externally publishedYes

Keywords

  • μ-Opioid receptor
  • Exon
  • G-protein activation
  • Knockout mice
  • Spinal cord

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Mizoguchi, H., Wu, H. E., Narita, M., Sora, I., Hall, F. S., Uhl, G. R., Loh, H. H., Nagase, H., & Tseng, L. F. (2003). Lack of μ-opioid receptor-mediated G-protein activation in the spinal cord of mice lacking exon 1 or exons 2 and 3 of the MOR-1 gene. Journal of Pharmacological Sciences, 93(4), 423-429. https://doi.org/10.1254/jphs.93.423