Na⁺/Ca²⁺ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility
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The Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca<sup>2+</sup> concentrations. NCX is critical for Ca<sup>2+</sup> 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 <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.
- Journal of Pharmacological Sciences
Journal of Pharmacological Sciences 123(3), 235-245, 2013
The Japanese Pharmacological Society