title: Na⁺/Ca²⁺ exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility.
abstract: The Na⁺/Ca²⁺ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca²⁺ concentrations. NCX is critical for Ca²⁺ 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 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.
authors.affiliation: Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Science, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Yasu-Taka
authors.initials: YT
authors.lastname: Azuma
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
authors.forename: Naoki
authors.initials: N
authors.lastname: Azuma
authors.forename: Satomi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000235:genetics* / Q000502:physiology; D006579:Heterozygote; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001565:Benzoates; D001593:Benzyl Compounds; D007093:Imidazoles; C499849:NCX1 protein, mouse; C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D002118:Calcium