Na+/Ca2+ exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo

Y. T. Azuma, S. Hayashi, K. Nishiyama, S. Kita, K. Mukai, H. Nakajima, T. Iwamoto, T. Takeuchi

研究成果: ジャーナルへの寄稿学術誌査読

14 被引用数 (Scopus)

抄録

Background: For the contraction and relaxation of gastric smooth muscles to occur, the intracellular Ca2+ concentration must be increased and decreased, respectively. The Na+/Ca2+ exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca2+ concentrations. Methods: To determine the role of NCX in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in NCX1 and NCX2 heterozygote knockout mice (HET). Key Results: The myenteric plexus layers and the longitudinal and circular muscle layers in the gastric fundus of wild-type mice (WT) were strongly immunoreactive to NCX1 and NCX2. EFS induced a transient relaxation that was apparent during the stimulus and a sustained relaxation that persisted after the end of the stimulus. The amplitudes of EFS-induced transient relaxation and sustained relaxation were greater in NCX1 HET and NCX2 HET than in WT. When an inhibitor of nitric oxide synthase was added following the EFS, neither NCX1 HET nor NCX2 HET exhibited transient relaxation, similar to WT. Furthermore, when a PACAP antagonist was added following the EFS, sustained relaxation in NCX1 HET and NCX2 HET was not observed, similar to WT. Next, we examined the effect of NCX heterozygous deficiency on relaxation in response to NO and PACAP in smooth muscles. The magnitude of NOR-1- and PACAP-induced relaxations in NCX1 HET and NCX2 HET was similar to that of WT. Conclusions & Inferences: In this study, we demonstrate that NCX1 and NCX2 expressed in neurons regulate the motility in the gastric fundus. When an inhibitor of nitric oxide synthase was added following the EFS, neither NCX1 HET nor NCX2 HET exhibited transient relaxation, similar to WT. Furthermore, when a PACAP antagonist was added following the EFS, sustained relaxation in NCX1 HET and NCX2 HET was not observed, similar to WT.

本文言語英語
ページ(範囲)827-836
ページ数10
ジャーナルNeurogastroenterology and Motility
28
6
DOI
出版ステータス出版済み - 6月 1 2016
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 内分泌系および自律システム
  • 消化器病学

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