Implication of the Descending Dynorphinergic Neuron Projecting to the Spinal Cord in the (+)-Matrine-and (+)-Allomatrine-Induced Antinociceptive Effects(Medicinal Chemistry)
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概要
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We previously reported that either (+)-matrine (matridin-15-one) or (+)-allomatrine (the C-6 epimer of matrine)-induced antinociceptive effect was attenuated by s.c. pretreatment with a κ-opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI), indicating the critical role of KORs in antinociceptive effects induced by these alkaloids. In the present study, we found that i.c.v. administration of either (+)-matrine- or (+)-allomatrine induced antinociceptive effects in the mouse tail-flick and warm-plate test, whereas these alkaloids when given spinally failed to induce antinociception. In the guanosine-5′-O-(3-[^<35>S]thio) trisphosphate ([^<35>S]GTPγS) binding assay, we demonstrated that neither (+)-matrine nor (+)-allomatrine produced the stimulation of [^<35>S]GTPγS binding in the membranes of the spinal cord, indicating that (+)-matrine- and (+)-allomatrine-induced supraspinal antinociceptive actions was not due to a direct stimulation of KORs by these alkaloids. Therefore, we next investigated the involvement of dynorphin A (1-17) release at the spinal or supraspinal site in (+)-matrine- or (+)-allomatrine-induced antinociception. The i.c.v. pretreatment with an antiserum against dynorphin A (1-17) could not affect the antinociceptive effect induced by s.c. treatment of (+)-matrine. In contrast, the s.c.-administered (+)-matrine- and (+)-allomatrine-induced antinociceptive effect was significantly attenuated by i.t. pretreatment of an antiserum against dynorphin A (1-17). The present data suggest that either (+)-matrine or (+)-allomatrine when given i.c.v. may stimulate the descending dynorphinergic neuron, resulting in the stimulation of KORs in the spinal cord, and this phenomenon in turn produces the antinociception in mice.
- 公益社団法人日本薬学会の論文
- 2005-05-01
著者
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SUZUKI Tsutomu
Department of Applied and Environmental Chemistry, Kitami Institute of Technology
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Sawaguchi T
Department Of Emergency Medicine Tokyo Women's Medical University
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NARITA Minoru
Department of Toxicology, School of Pharmacy, Hoshi University
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KAMEI Junzo
Department of Pathophysiology, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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YAMAUCHI Takayasu
Faculty of Medicinal Chemistry; Hoshi University
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HIGASHIYAMA Kimio
Institute of Medicinal Chemistry, Hoshi University
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Kamei Junzo
Department Of Pathophysiology And Therapeutics Faculty Of Pharmaceutical Sciences Hoshi University
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Kamei Junzo
Department Of Pathophysilology & Therapeutics Faculty Of Pharmaceutical Sciences Hoshi Universit
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Nomura Mutsuko
Department Of Toxicology Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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TAKEUCHI Yosuke
Institute of Medicinal Chemistry, Hoshi University
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YAMAUCHI Takayasu
Institute of Medicinal Chemistry, Hoshi University
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IMAI Satoshi
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences
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YAJIMA Yoshinori
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences
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Takeuchi Yosuke
Institute Of Medicinal Chemistry Hoshi University
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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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Higashiyama Kimio
Institute Of Medicinal Chemistry Hoshi University
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Yamauchi Takayasu
Institute Of Medicinal Chemistry Hoshi University
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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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Yajima Yoshinori
Department Of Toxicology Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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Imai Satoshi
Department Of Dermatology University Of Occupational And Environmental Health
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Imai Satoshi
Department Of Toxicology Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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Higashiyama K
Faculty Of Pharmaceutical Sciences Okayama University
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Kamei Junzo
Department Of Pathophysiology & Therapeutics School Of Pharmacy And Pharmaceutical Sciences Hosh
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Suzuki Tsutomu
Department Of Applied And Environmental Chemistry Kitami Institute Of Technology
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