ISSN 1300-4948 | E-ISSN 2148-5607
Basic & Translational - Original Article
TRPA1 and substance P mediate stress induced duodenal lesions in water immersion restraint stress rat model
Yan Xu 1 ,  
Hui Deng 3 ,  
Ji Jia 3 ,  
Jing Yang 3 ,  
1 Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command; The 173rd Clinical Department of PLA 421rd Hospital, Guangdong, China  
2 The 173rd Clinical Department of PLA 421rd Hospital, Guangdong, China  
3 Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangdong, China  
Turk J Gastroenterol 2018; 29: 692-700
DOI: 10.5152/tjg.2018.17817
Key Words: Duodenal lesions, TRPA1, substance P, stress, inflammation, neuroimmune
Abstract

 

Background/Aims: Transient receptor potential ankyrin 1 (TRPA1) and substance P (SP), both expression in sensory neurons, have important roles in stress-induced duodenal lesions. The possible contribution of TRPA1 and SP to stress-induced duodenal lesions was explored by using the water immersion restraint stress (WIRS) rat model.

 

Materials and Methods: Western blotting, Real-time polymerase chain reaction (RT-PCR), and immunohistochemistry assay were used to evaluate the changes of TRPA1and SP expression in the dorsal root ganglia (DRG, T8-11), the corresponding segment of the spinal cord (T8-11), and the duodenum in a duodenal lesions rat model. The SP concentrations of duodenal mucosa were investigated using an enzyme-linked immunosorbent assay (ELISA). Duodenal lesions were assessed according to histopathological changes. TRPA1 specific antagonist HC-030031 was intrathecally or intraperitoneally performed to suppress the expression of both TRPA1 and SP for evaluating the roles of TRPA1 and SP in duodenal lesions.

 

Results: In contrast to the control group, TRPA1 and substance P in the DRG (T8-11) and duodenum were up-regulated, and concentrations of SP in the duodenal mucosa were increased after WIRS (p<0.05), which are closely associated with duodenal lesions. SP concentrations in the duodenal mucosa were decreased and duodenal lesions were alleviated by pretreatment with TRPA1 antagonist HC-030031. We identified a protective role for HC-030031 in WIRS-induced duodenal lesions. Furthermore, we demonstrated that WIRS increased the concentrations of SP in the duodenal mucosa in a TRPA1-dependent manner. However, WIRS caused no significant changes of TRPA1 and SP in the spinal cord (T8-11) compared with the control group (p>0.05).

 

Conclusion: Our study indicates that TRPA1 antagonist HC-030031 alleviates duodenal lesions. TRPA1 is activated and sensitized, therefore concomitant neuropeptide SP is released, which exerts a critical role in inducing and maintaining duodenal lesions following WIRS in rats. This provides evidence that neuroimmune interactions may control duodenal injury. TRPA1 may be a potential drug target to inhibit the development of duodenal lesions by stress-induced in patients.

 

 

 

Cite this article as: Xu Y, Huang C, Deng H, et al. TRPA1 and substance P mediate stress induced duodenal lesions in water immersion restraint stress rat model. Turk J Gastroenterol 2018; 29: 692-700.

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AVES | Copyright © 2018 Turkish Society of Gastroenterology | Latest Update: 22.10.2018