APETx2 regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome mice through 5-HT signalling pathway

OBJECTIVES: To investigate whether APETx2, a potent and selective inhibitor of ASIC3, regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome (PI-IBS) mice through the 5-HT signalling pathway. METHODS: The PI-IBS model was established by Trichinella spiralis infection of NIH mice. APETx2(120 µg/kg) was administrated to PI-IBS mice by intraperitoneal injection once a day, lasting for 7 days. The gastrointestinal function of mice was assessed by the time of the first dark stool and the number of pellets defecated within 2 h. The visceral sensitivity was tested via abdominal withdrawal reflex. The protein levels of 5-HT and CRF in colon tissues were detected by immunohistochemistry. The changes in serum 5-HT and colon CRF contents were detected by ELISA. The mRNA levels of colon 5-HT4R and CRF were detected by RT-qPCR. The protein levels of colon 5-HT4R and dorsal root ganglion (DRG) ASIC3 were detected by Western blotting. KEY FINDINGS: The results indicated that APETx2 could markedly improve gastrointestinal function and visceral sensitivity in mice. Moreover, APETx2 could reduce the expression level of ASIC3 protein in the DRG of PI-IBS mice. APETx2 could increase the expression levels of 5-HT in serum and colon, CRF and 5-HT4R in the colon, and 5-HT4R in brain tissue in PI-IBS mice. CONCLUSIONS: APETx2 can improve visceral sensitivity and intestinal motility in PI-IBS through 5-HT signalling pathway.