Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility
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概要
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The Na+/Ca2+ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca2+ concentrations. NCX is critical for Ca2+ regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. To determine the role of NCX1 and NCX2 in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced responses in the longitudinal smooth muscle of the distal colon in NCX1 and NCX2 double-heterozygote knockout mice (Double HET). We found that the amplitudes of EFS-induced relaxation that persisted during EFS were greater in Double HET than in wild-type mice (WT). Under the non-adrenergic, non-cholinergic (NANC) condition, EFS-induced relaxation in Double HET was similar in amplitude to that of WT. In the experiments in which <span style="font-variant: small-caps;">l</span>-NNA was added under NANC conditions following the EFS, the magnitudes of EFS-induced relaxation were smaller in Double HET than those in WT. In addition, an NCX inhibitor, SN-6, enhanced EFS-induced relaxation but did not affect EFS-induced relaxation under NANC condition, as in Double HET. Moreover, the magnitudes of relaxation induced by NOR-1, which generates NO, were greater in Double HET compared with WT. Similarly, SN-6 potentiated the magnitudes of NOR-1–induced relaxation. In this study, we demonstrate that NCX regulate colonic motility by altering the sensitivity of the inhibitory component.
- 公益社団法人 日本薬理学会の論文
著者
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Kita Satomi
Department Of Pharmacology Faculty Of Medicine Fukuoka University
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Iwamoto Takahiro
Department Of Medical Engineering And Cardiology Institute Of Development Aging And Cancer Tohoku Un
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Azuma Yasu-taka
Laboratory Of Veterinary Pharmacology Division Of Veterinary Science Osaka Prefecture University Gra
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Takeuchi Tadayoshi
Laboratory Of Veterinary Pharmacology Division Of Veterinary Science Osaka Prefecture University Gra
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Nakajima Hidemitsu
Laboratory Of Veterinary Pharmacology Division Of Veterinary Science Osaka Prefecture University Gra
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Hayashi Satomi
Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Japan
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Iwamoto Takahiro
Department of Pharmacology, Faculty of Medicine, Fukuoka University, Japan
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Kita Satomi
Department of Pharmacology, Faculty of Medicine, Fukuoka University, Japan
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Azuma Naoki
Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Japan
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Nishiyama Kazuhiro
Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Japan
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