Direct Inhibition of N-Methyl-D-Aspartate (NMDA)-Receptor Function by Antiglaucomatous β-Antagonists
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概要
- 論文の詳細を見る
In the present study, we investigated the direct effects of antiglaucoma drugs (timolol, betaxolol, pilocarpine, and latanoprost) on N-methyl-<sc>D</sc>-aspartate (NMDA)-receptor function using a Xenopus oocytes expression system and electrophysiological techniques. In oocytes expressing wild-type NMDA (NR1a/NR2A) receptors, timolol and betaxolol significantly inhibited glutamate-evoked currents, whereas less inhibition was obtained with pilocarpine, and latanoprost had few effects. Moreover, the effect of timolol and betaxolol was noncompetitive with respect to glutamate. Mutations that changed Asn616 of the NR1a subunit, a critical residue for Mg2+ blocking of NMDA receptors, to Arg (N616R) or Gln (N616Q) almost eliminated the inhibitory effects of timolol and betaxolol, as well as the blocking effect of Mg2+. Experiments were also carried out to examine the protective effects of timolol and betaxolol against death of oocytes expressing NMDA receptors. During incubation of oocytes, especially in Mg2+-free medium, cell death was induced by addition of glutamate because of the continuous activation of the NMDA receptors expressed. Timolol and betaxolol significantly improved oocyte viability when they were added during the incubation period. These results suggest that timolol and betaxolol may have an additional role that they directly inhibit NMDA-receptor function, possibly via N616 of the NR1a subunit.
- 社団法人 日本薬理学会の論文
- 2008-03-20
著者
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Tsutsui Masato
Department Of Pharmacology School Of Medicine University Of Occupational And Environmental Health
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Yanagihara Nobuyuki
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health
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KUBOTA Toshiaki
Department of Ophthalmology, Faculty of Medicine, Kyushu University
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MATSUMOTO TETSURO
Japanese Research Group for UTI
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TAWARA Akihiko
Department of Ophthalmology, School of Medicine, University of Occupational and Environmental Health
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Morita Hirofumi
Department Of Ophthalmology School Of Medicine University Of Occupational And Environmental Health
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Yanagihara Nobuyuki
Department Of Pharmacology School Of Medicine University Of Occupational And Environmental Health
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Yanagihara Nobuyuki
Department Of Phamacology University Of Occupational And Environmental Health
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Tsutsumi Masato
Department Of Cardiovascular Medicine Kyushu University Graduate School Of Medical Sciences
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Ueno Susumu
Department Of Phamacology University Of Occupational And Environmental Health
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Miura Tetsuya
Division Of Urology Kobe University Graduate School Of Medicine
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Tawara Akihiko
Department Of Ophthalmology School Of Medicine University Of Occupational And Environmental Health
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Tsutsui Masato
Department Of Dermatology Asahikawa Medical College
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Nakashima Yasuhide
Second Department Of Internal Medicine University Of Occupational And Environmental Health School Of
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TOYOHIRA Yumiko
Department of Phamacology, University of Occupational and Environmental Health
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NAGATA Tatsuo
Department of Ophthalmology, School of Medicine, University of Occupational and Environmental Health
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Kubota Toshiaki
Department Of Ophthalmology Faculty Of Medicine Kyushu University
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Nakashima Yasuhide
Department Of Pharmacology School Of Medicine University Of Occupational And Environmental Health
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Nagata Tatsuo
Department Of Ophthalmology School Of Medicine University Of Occupational And Environmental Health
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Toyohira Yumiko
Department Of Phamacology University Of Occupational And Environmental Health
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Tsutsui Masato
Department Of Pharmacology University Of Occupational And Environmental Health
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Matsumoto Tetsuro
Japanese Society Of Chemotherapy (jsc)
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Muratani Tetsuro
Department Of Urology University Of Occupational And Environmental Health
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Morita Hirohumi
Department of Ophthalmology, School of Medicine, University of Occupational and Environmental Health
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UENO Susumu
Department of Occupational Toxicology, University of Occupational and Environmental Health
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TSUTSUI Masato
Department of Cardiology, Iizuka Hospital
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UENO Susumu
Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
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