Premium
Ablation of Tacr2 in mice leads to gastric emptying disturbance
Author(s) -
Mao Y.L.,
Shen C.L.,
Zhou T.,
Ma B.T.,
Tang L.Y.,
Wu W.T.,
Zhang H.X.,
Lu H.L.,
Xu W.X.,
Wang Z.G.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13117
Subject(s) - vasoactive intestinal peptide , knockout mouse , nitric oxide , medicine , gastric emptying , endocrinology , stomach , myenteric plexus , interstitial cell of cajal , receptor , nitric oxide synthase , stimulation , biology , chemistry , neuropeptide , immunohistochemistry
Background Tacr2 is one of the G protein‐coupled receptors( GPCR s) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal ( GI ) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. Methods The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2 ‐null mice were analyzed and compared with their wild type (wt) littermates. Key Results Increased food retention was detected in Tacr2 −/− mice. The stomach of Tacr2 −/− mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation ( EFS )‐induced inhibition in the gastric fundus and decreased frequency of migrating motor complex ( MMC ), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up‐regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2 −/− mice. Intraperitoneal application of 7‐nitroindazole (7‐ NI ) to Tacr2 −/− mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF ‐κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. Conclusions & Inferences Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP , enhanced NO signaling and changed the Creb and NF ‐κB signalings, finally leading to the gastric emptying disturbance of Tacr2 −/− mice.