title: Roles of Na(+)/Ca(2+) exchanger isoforms NCX1 and NCX2 in motility in mouse ileum.
abstract: The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan. azuma@vet.osakafu-u.ac.jp.
authors.forename: Yasu-Taka
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, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Morioka
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Natsuho
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Teramoto
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Tanioka
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Satomi
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, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Satomi
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, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Takahiro
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, 1-58 Rinku-ohraikita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects; D005838:Genotype; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D010641:Phenotype; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology
chemical_list: C499849:NCX1 protein, mouse; C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; D013373:Substance P; D000109:Acetylcholine
keywords: Acetylcholine; Contraction; Ileum; Longitudinal smooth muscles; Na+/Ca2+ exchanger