title: Na(+) /Ca(2+) exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo.
abstract: For the contraction and relaxation of gastric smooth muscles to occur, the intracellular Ca(2+) concentration must be increased and decreased, respectively. The Na(+) /Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations.
  
  
  
  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).
  
  
  
  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.
  
  
  
  In this study, we demonstrate that NCX1 and NCX2 expressed in neurons regulate the motility in the gastric fundus.
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: Y T
authors.initials: YT
authors.lastname: Azuma
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kita
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mukai
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D005748:Gastric Fundus / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology*; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000502:physiology*; D009924:Organ Culture Techniques; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C499849:NCX1 protein, mouse; C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger
keywords: Na+/Ca2+ exchanger; gastric fundus; gastric motility; myenteric plexus; relaxation