Overexpression of Na+/Ca2+ exchanger 1 display enhanced relaxation in the gastric fundus

Abstract

In gastric smooth muscles, the released Ca activates the contractile proteins and Ca taken up from the cytosol cause relaxation. The Na/Ca exchanger (NCX) is an antiporter membrane protein that controls Ca influx and efflux across the membrane. However, the possible relation of NCX in gastric fundus motility is largely unknown. Here, we investigated electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in smooth muscle-specific NCX1 transgenic mice (Tg). EFS caused a bi-phasic response, transient and sustained relaxation. The sustained relaxation prolonged for an extended period after the end of the stimulus. EFS-induced transient relaxation and sustained relaxation were greater in Tg than in wild-type mice (WT). Disruption of nitric oxide component by N-nitro-l-arginine, EFS-induced transient and sustained relaxations caused still marked in Tg compared to WT. Inhibition of PACAP by antagonist, EFS-induced sustained relaxation in Tg was not seen, similar to WT. Nevertheless, transient relaxation remained more pronounced in Tg than in WT. Next, we examined responses to NO and PACAP in smooth muscles. The magnitudes of NOR-1, which generates NO, and PACAP-induced relaxations were greater in Tg than in WT. In this study, we demonstrate that NCX1 regulates gastric fundus motility.

Presence and Effects of Pituitary Adenylate Cyclase Activating Polypeptide Under Physiological and Pathological Conditions in the Stomach

“…PACAP also inhibits relaxation in the porcine lower esophageal sphincter ( 82 ). A recent study has confirmed the relaxant activity of PACAP in a dose dependent manner in mouse gastric fundus, while PACAP6–38 suppresses gastric relaxation ( 83 ). Evidence has also been published for the involvement of VIP/PACAP receptors in the afferent pathway mediating surgery-induced fundic relaxation in the rat ( 84 ) (Figure 1 ).…”

A Calcium/Cation Exchanger Participates in the Programmed Cell Death and in vitro Virulence of Entamoeba histolytica

“…This hypothesis is supported by: (i) the expression level of this protein is higher in the pathogenic E. histolytica than in the non-pathogenic E. dispar ; and (ii) the overexpression of EhCCX augmented the in vitro virulence properties of trophozoites, such as phagocytosis, destruction of mammalian cell monolayers and migration. Similarly, the overexpression of NCX proteins enhances the heart rate mediated by beta-adrenergic (Kaese et al, 2017 ), and the relaxation of gastric fundus (Fujimoto et al, 2016 ). We are hypothesizing that, as calcium/cation exchangers can reverse the ions transport under certain conditions (Harper and Sage, 2016 ), the different stimuli that are involved in the E. histolytica virulence could increase the Ca 2+ influx via EhCCX, extending the period of high Ca 2+ levels in cytoplasm, maintaining the response to the signal.…”

Na⁺/Ca²⁺ exchanger contributes to stool transport in mice with experimental diarrhea

“…Ex vivo motility was analyzed using previously described methods [ 7 ]. Briefly, the proximal and transverse colons were removed from mice (10–15 weeks old).…”

“…The functional roles by which NCX influences gastrointestinal motility including contraction and relaxation are incompletely understood and vary by tissue, although its role in cardiac muscle and brain neurons is well understood. Our group is showing to reveal the functional role of NCX on gastrointestinal motility, because Ca 2+ homeostasis is central to the regulation of gastrointestinal smooth muscle functions [ 1 , 4 , 7 , 12 , 13 , 14 ]. To specifically assess the physiological role of NCX, we used NCX1 heterozygote knockout mice (NCX1 HET) and NCX2 HET.…”