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
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概要
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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 (<sc>D</sc>-Ala2,N-MePhe 4,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 [<sc>D</sc>-Pen 2,5]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.
- 社団法人 日本薬理学会の論文
- 2003-12-01
著者
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Nagase H
Basic Research Laboratories Toray Industries Inc.
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Nagase Hiroshi
Pharmaceutical Research Laboratories Toray Industries Inc.
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Uhl G
National Inst. Health
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Tseng L
Department Of Anesthesiology Medical College Of Wisconsin
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Tseng Leon
Department Of Anesthesiology Medical College Of Wisconsin
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Uhl George
Molecular Neurobiology Branch Intramural Research Program National Institute On Drug Abuse National
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NARITA Minoru
Department of Toxicology, School of Pharmacy, Hoshi University
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MIZOGUCHI Hirokazu
Department of Physiology and Anatomy, Tohoku Pharmaceutical University
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WU Hsiang-En
Department of Anesthesiology, Medical College of Wisconsin
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SORA Ichiro
Department of Psychopharmacology, Tokyo Institute of Psychiatry
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HALL F.
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Nation
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LOH Horace
Department of Pharmacology, University of Minnesota Medical School
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Sora Ichiro
Department Of Psychopharmacology Tokyo Institute Of Psychiatry
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Nomura Mutsuko
Department Of Toxicology Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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Loh Horace
Department Of Pharmacology University Of Minnesota Medical School
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Wu Hsiang-en
Department Of Anesthesiology Medical College Of Wisconsin
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Sora Ichiro
Department Of Internal Medicine General Minami Tohoku Hospital
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Namiki Mizuho
Dep. Of Emergency Medicine Tokyo Women's Medical Univ. Jpn
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Namiki Mizuho
Department Of Emergency Medicine Tokyo Women's Medical University
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Narita Minoru
Department Of Emergency Medicine Tokyo Women's Medical University
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Mizoguchi Hirokazu
Department Of Anesthesiology Medical College Of Wisconsin
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Narita Minoru
Department Of Anesthesiology Medical College Of Wisconsin
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Nomura Mutsuko
Department Of Emergency Medicine Tokyo Women's Medical University
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Sora Ichiro
Department Of Biology Psychiatry Tohoku University Graduate School Of Medicine Tohoku University
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Hall F.
Molecular Neurobiology Branch Intramural Research Program National Institute On Drug Abuse National
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Sora Ichiro
Department of Biological Psychiatry, Graduate School of Medicine, Tohoku University
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- Potential Anxiolytic and Antidepressant-Like Activities of SNC80, a Selective δ-Opioid Agonist, in Behavioral Models in Rodents
- 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
- TRK-820, a Selective к-Opioid Agonist, Produces Potent Antinociception in Cynomolgus Monkeys