Na+/Ca2+ exchanger 2‐heterozygote knockout mice display decreased acetylcholine release and altered colonic motility in vivo

Azuma, Yasutaka; Nishiyama, Kazuhiro; Kita, Satomi; Komuro, Issei; Nakajima, Hidemitsu; Iwamoto, Takahiro; Takeuchi, Tadayoshi

doi:10.1111/nmo.12029

Cited by 20 publications

(35 citation statements)

References 43 publications

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“…On the other hand, the magnitudes of EFS-induced relaxation were greater in Double HET (Fig. 2C) compared with NCX1 HET (15). There is a significant change between EFS-induced relaxation in Double HET and that in NCX1 HET.…”

Section: +mentioning

confidence: 72%

“…5B). In contrast, NCX2 HET exhibited magnitudes of NOR-1-induced relaxation similar to those of WT (15). We have already demonstrated that NCX2 HET showed enhanced amplitudes of EFS-induced relaxation by decreasing ACh release (15).…”

Section: +mentioning

confidence: 90%

“…NCX1 heterozygous and NCX2 heterozygous mice appeared healthy and were comparable in colonic motility to wild-type mice. Our immunohistochemical results have previously provided evidence indicating the presence of expression of NCX1 and NCX2 in the longitudinal and circular muscle layers and in the myenteric plexus layers of the distal colon (15). We also have previously demonstrated that NCX2 heterozygous mice, but not NCX1 heterozygous mice, display altered colonic motility (15).…”

Section: Introductionmentioning

confidence: 85%

“…One key result is that the expression levels of NCX1 and NCX2 in Double HET account for 29% and 36% of the levels in WT, respectively. In the previous report, enhanced NOR-1-induced relaxation is not pronounced in NCX1 and NCX2 heterozygous mice, as the expression level of NCX1 in NCX1 heterozygous mice and the expression level of NCX2 in NCX2 heterozygous mice, respectively, account for 60% and 57% of the levels in WT (15). There is a possibility that lower expressions of NCX1 and NCX2 caused the decrease in functional coupling and/or collaborative functions between NCX1 and NCX2 in Double HET compared with those in each single HET.…”

Section: Discussionmentioning

confidence: 99%

“…One possible explanation is the decreased release of excitatory mediators such as ACh from neurons. NCX2 heterozygous mice have previously displayed decreased release of ACh in the distal colon segments (15), suggesting that Double HET regulates colonic motility by altering ACh release onto the myenteric neurons of the distal colon. Moreover, gastrointestinal tract motility can be regulated by sensitivity to mediators of the smooth muscle cells in addition to the release of mediators from myenteric neurons.…”

Section: Discussionmentioning

confidence: 99%

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Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility

et al. 2013

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Abstract. The Na + /Ca 2+ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca 2+ concentrations. NCX is critical for Ca 2+ 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, noncholinergic (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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Section: +mentioning

confidence: 72%

Section: +mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility

et al. 2013

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Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Nishiyama

Aono

Fujimoto

et al. 2018

Journal Cellular Physiology

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Organ-organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation.Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.

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Roles of Na+/Ca2+ exchanger isoforms NCX1 and NCX2 in motility in mouse ileum

Nishiyama

Azuma

Morioka

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Na⁺/Ca²⁺ exchanger 2‐heterozygote knockout mice display decreased acetylcholine release and altered colonic motility in vivo

Abstract: In this study, we demonstrate that NCX2 regulates colonic motility by altering ACh release onto the myenteric neurons of the distal colon.

Cited by 20 publications

References 43 publications

Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility

Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility

Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Roles of Na+/Ca2+ exchanger isoforms NCX1 and NCX2 in motility in mouse ileum

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