Inhibitory Actions of Indomethacin on Electrical and Mechanical Responses Produced by Nerve Stimulation in Circular Smooth Muscle of the Guinea-Pig Gastric Fundus
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概要
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The effects of indomethacin on electrical and mechanical responses produced by transmural nerve stimulation (TNS) were investigated in isolated circular smooth muscle of the guinea-pig gastric fundus. TNS evoked a cholinergic excitatory junction potential (e.j.p.). The e.j.p.s were inhibited by 1-10 μM indomethacin, in a concentration-dependent manner, with no marked alteration of the resting membrane potential. Exogenously applied acetylcholine caused a depolarization of the membrane that was not altered by indomethacin. TNS evoked a cholinergic twitch contraction at low frequencies (0.1 Hz). A train of TNS's at high frequency (1 Hz) produced a transient contraction with a subsequent sustained relaxation. Indomethacin reduced the resting tension and inhibited these TNS-induced contractions. Application of N^ω-nitro-L-arginine (NOLA), an inhibitor of nitric oxide (NO) synthesis, increased the amplitude of twitch contractions, and altered transient contractions to tetanic contractions during TNS at a frequency of 1 Hz, also with an increased amplitude. In the presence of NOLA, indomethacin (5 μM) again reduced the resting tension and inhibited TNS-induced contractions. This inhibition was greater for twitch contractions than for tetanic contractions. Nifedipine reduced the TNS-induced contractions, while addition of indomethacin further reduced the amplitude of contractions. Contractions produced by low concentrations of acetylcholine (0.1 μM) were inhibited by indomethacin, while those produced by 1 μM were not. These results indicate that the inhibitory actions of indomethacin on TNS-induced contractions do not involve enhanced production of NO or selective inhibition of voltage-gated Ca-channels. Prejunctional autoregulatory mechanisms may also not be altered by indomethacin. As indomethacin inhibits the enzyme cyclooxygenase, it is speculated that endogenously produced prostaglandins exert excitatory actions on gastric smooth muscle, and act mainly postjunctionally to facilitate spontaneous and neurogenic electrical and mechanical activity.
- 日本平滑筋学会の論文
著者
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SUZUKI Hikaru
Department of Physiology, Nagoya City University Medical School
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KITO Yoshihiko
Department of Physiology, Nagoya City University Medical School
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Yoneda Satoshi
Department Of Thoracic Surgery Imakiire General Hospital
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Yoneda Satoshi
Department Of Physiology Nagoya City University Medical School:(present)department Of Physiology Ii
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Kito Yoshihiko
Department Of Gastroenterology And Metabolism Nagoya City University Graduate School Of Medical Scie
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Suzuki Hikaru
Department Of Cell Physiology Nagoya City University Medical School
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Kito Y
Department Of Gastroenterology And Metabolism Nagoya City University Graduate School Of Medical Scie
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Yoneda Satoshi
Department Of Applied Chemistry Faculty Of Engineering Kyushu Institute Of Technology
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Suzuki Hikaru
Department Of Cardiology Tokyo Women's Medical University
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KITO Yoshihiko
Department of Cell Physiology, Nagoya City University Medical School
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