Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model

Xu, Yan; Jia, Ji-dong; Xie, Chuangbo; Wu, Yi; Tu, Weifeng

doi:10.1159/000484980

Cited by 11 publications

(16 citation statements)

References 38 publications

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“…It has been reported that substance P may initiate the earliest changes observed in blood-brain barrier permeability (40). In addition, it has also been documented that TRPA1 mediates the development of gastric mucosal and duodenal lesions in a water immersion restraint stress rat model by promoting the release of substance P (22,41). Since TRPA1 is involved in Ca 2+ influx and increases in tight junction permeability (42), TRPA1 may contribute to damage in epithelial barrier function by regulating oxidative stress induced by stress.…”

Section: Discussionmentioning

confidence: 99%

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Luo

Niu

et al. 2021

Exp Ther Med

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Stress induced by changes in the internal or external environment in humans and animals leads to intestinal epithelial damage, in a manner that is associated with impaired intestinal barrier function. However, the role of the stress hormone norepinephrine (NE) in impairments in barrier function remains poorly understood. In the present study, a rat heat-exposed model was used to observe changes in the tight junction proteins Occludin and zonula occludens-1 (ZO-1), in addition to those in protease-activated receptor 2 (PAR-2) and transient receptor potential ankyrin 1 channel (TRPA1) in colon. The levels of plasma NE were detected using an ELISA kit. Different concentrations of NE were used to culture the human colon cell line Caco-2 for 6 and 24 h to investigate the cell viability using Cell Counting Kit-8 assay, whilst the expression levels of Occludin, ZO-1, PAR-2 and TRPA1 were examined using western blotting and immunofluorescence in Caco-2 cells and immunohistrochemistry in rat colon tissues. Although there was no clear histological damage to the rat colonic mucosa, there were decreased expression levels of tight junction proteins Occludin and ZO-1 after heat exposure. In addition, PAR-2 expression was increased by heat exposure. It was found that TRPA1 expression was concentrated to the luminal surface of the colon in the heat exposed group compared with that in the control group. After the administration of increasing concentrations of NE for 6 h, treatment did not affect cell viability. Furthermore, after application of NE for 24 h, cell viability gradually increased as the NE concentration was elevated from 10 to 100 µM. However, no significant increase in viability was observed when the cells were treated with 120 and 160 µM NE. Occludin expression was decreased when 10 µM NE was applied for 6 or 24 h. By contrast, 60 µM NE significantly downregulated Occludin expression in the 6 h group, but caused an insignificant decrease in the 24 h group. It was found that ZO-1 expression was upregulated after treatment with 10 µM NE for 6 h, whilst downregulation was observed after treatment with 10 µM NE for 24 h. PAR-2 protein expression was increased after application of NE for both 6 and 24 h, but not after treatment with 60 µM NE. In addition, TRPA1 expression was not affected by the treatment of NE, but increased positive staining was observed on the luminal side of the mucosa, which appeared to be concentrated in the cells of the luminal side in the rat colon after heat exposure. Collectively, the present results suggested that expression of tight junction proteins Occludin and ZO-1, in addition to that of PAR-2, can be regulated by NE, which may contribute to impairments in barrier function observed during heat stress.

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Section: Discussionmentioning

confidence: 99%

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Luo

Niu

et al. 2021

Exp Ther Med

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“…In this study, we chose a rabbit extracellular TRPA1 antibody for several reasons: (1) this antibody has been well characterized by the vendor, demonstrating a high specificity against an epitope (NSTGIINETSDHSE) corresponding to amino acid residues 747 to 760 in the first extracellular loop of TRPA1 ( Figure 1a); (2) the specificity has been verified in TRPA1 knockout tissue; 38 and (3) it consistently detects TRPA1 expression by IHC or immunoblot from DRGs and from nonneuronal tissues. 19,[36][37][38]40,[53][54][55][56][57][58][59][60][61][62][63] We also tested the specificity of this antibody in the detection of TRPA1 expression. By immunoblot, the antibody revealed a clean band at $120 KDa as the target protein in the homogenates of the DRGs from adult rats, and preincubation with excess immunogenic peptide completely eliminated the band (Figure 1b).…”

Section: Trpa1 Is Expressed In Primary Sensory Neurons Sgcs and Scsmentioning

confidence: 99%

Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain

et al. 2020

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Transient receptor potential ankyrin 1 (TRPA1) is well documented as an important molecule in pain hypersensitivity following inflammation and nerve injury and in many other cellular biological processes. Here, we show that TRPA1 is expressed not only by sensory neurons of the dorsal root ganglia (DRG) but also in their adjacent satellite glial cells (SGCs), as well as nonmyelinating Schwann cells. TRPA1 immunoreactivity is also detected in various cutaneous structures of sensory neuronal terminals, including small and large caliber cutaneous sensory fibers and endings. The SGC-expressed TRPA1 is functional. Like DRG neurons, dissociated SGCs exhibit a robust response to the TRPA1-selective agonist allyl isothiocyanate (AITC) by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses are abolished by the TRPA1 antagonist HC030031 and are absent in SGCs and neurons from global TRPA1 null mice. SGCs and neurons harvested from DRG proximal to painful tissue inflammation induced by plantar injection of complete Freund’s adjuvant show greater AITC-evoked elevation of [Ca2+]i and slower recovery compared to sham controls. Similar TRPA1 sensitization occurs in both SGCs and neurons during neuropathic pain induced by spared nerve injury. Together, these results show that functional TRPA1 is expressed by sensory ganglia SGCs, and TRPA1 function in SGCs is enhanced after both peripheral inflammation and nerve injury, and suggest that TRPA1 in SGCs may contribute to inflammatory and neuropathic pain.

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“…Propolis extracts usually have an intense odor and pungent taste. The pungent taste accounts for APC ligation to transient receptor potential channel ankyrin 1 (TRPA1) [324], which are abundant in the stomach and involved in stress-induced gastric mucosal lesions [325]. Hence, one should make efforts to exclude the “side effects” of propolis by using more adequate controls.…”

Section: Perspectivesmentioning

confidence: 99%

Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models

Kitamura

2019

Molecules

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Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.

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Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model

Cited by 11 publications

References 38 publications

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain

Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models

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