Recent Advances in the Search for the μ-Opioidergic System : Endomorphin-induced Motivational Effect : Differential Mechanism of Endomorphin-1 and Endomorphin-2
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概要
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The newly discovered endogenous μ-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. This review focuses on differential mechanism of the motivational effects induced by EM-1 and EM-2. In the [35S]GTPγS binding assay, either EM-1 or EM-2 causes a concentration-dependent G-protein activation in brain membrane of normal mice, whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes obtained from the MOP-R knockout mice. These results provide direct evidence at the molecular level that both EMs act on the MOP-R as the endogenous MOP-R agonists. Based on the conditioned place preference paradigm in mice, EM-1 given intracerebroventriculally produced a dose-related place preference. This effect was abolished by pretreatment with the MOP-R antagonist β-funaltrexamine (FNA) but not the δ-opioid receptor (DOP-R) antagonist naltrindole and the κ-opioid receptor (KOP-R) antagonist nor-bialtorphimine (BNI). Unlike EM-1, EM-2 exhibited a place aversion. The aversive effect was inhibited by not only β-FNA but also nor-BNI. Place aversion produced by EM-2 was also attenuated by pretreatment with an antiserum against an endogenous KOP-R ligand dynorphin A(1 – 17). These findings indicate that EM-1 may produce its rewarding effect via MOP-Rs. Furthermore, the aversive effect induced by EM-2 may be associated with the stimulation of the EM-1-insensitive MOP-R subtype and necessarily activate an endogenous KOPergic system in the mouse brain.
- 社団法人 日本薬理学会の論文
- 2002-07-01
著者
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SUZUKI Tsutomu
Department of Applied and Environmental Chemistry, Kitami Institute of Technology
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NARITA Minoru
Department of Toxicology, School of Pharmacy, Hoshi University
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Narita Minoru
Department Of Toxicology School Of Pharmacy Hoshi University
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OZAKI SATORU
Departments of Clinical Laboratory, National Kanazawa Hospital
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Ozaki Satoru
Department Of Toxicology School Of Pharmacy Hoshi University
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Narita Minoru
Department Of Anesthesiology Medical College Of Wisconsin
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