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

Autor:	Yasu-Taka Azuma, Kazuhiro Nishiyama, Takahiro Iwamoto, Hidemitsu Nakajima, Kazunori Mukai, Satomi Hayashi, Satomi Kita, Tadayoshi Takeuchi
Rok vydání:	2016
Předmět:	0301 basic medicine Heterozygote medicine.medical_specialty Pathology animal structures Contraction (grammar) Physiology Muscle Relaxation Gastric motility Motility Sodium-Calcium Exchanger Mice 03 medical and health sciences Organ Culture Techniques 0302 clinical medicine Internal medicine medicine Animals Gastric Fundus Gastrointestinal Transit Myenteric plexus Mice Knockout biology Endocrine and Autonomic Systems business.industry Gastroenterology Antagonist Mice Inbred C57BL Nitric oxide synthase 030104 developmental biology Endocrinology Knockout mouse cardiovascular system biology.protein Gastrointestinal Motility business 030217 neurology & neurosurgery Intracellular
Zdroj:	Neurogastroenterology & Motility. 28:827-836
ISSN:	1350-1925
DOI:	10.1111/nmo.12779
Popis:	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.
Databáze:	OpenAIRE
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