Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility
Kazuhiro NishiyamaYasu-Taka AzumaSatomi KitaNaoki AzumaSatomi HayashiHidemitsu NakajimaTakahiro IwamotoTadayoshi Takeuchi
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2013 Volume 123 Issue 3 Pages 235-245


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 knockoutmice (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 l-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.

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© 2013 The Japanese Pharmacological Society
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