Regulating effect of Epac1 on visceral hypersensitivity in rats and its mechanism
YANG Jing
LI Kun
LEI Xiaofei
YANG Hongli
LI Shuangling
XU Changqing
Abstract：Objective To investigate the regulating effect of Epac 1 on the visceral hypersensitivity in rats and its downstream mechanism .Methods Forty-five neonatal SD male rats were randomly divided into three groups: the control group, model group and CE3F4 group with 15 rats per group.Visceral hypersensitive model was established in the model group and CE3F4 group but not in the control group .At the age of 8 weeks, rats in the control group and model group were both injected by 25μL normal saline intrathecally , while CE3F4 group was injected by 25μL solution of Epac1 specific an-tagonist CE3F4 (0.2 nmol/μL).Three days after injection, AWR scores, pain threshold and maximal tolerance threshold at graded colorectal distension pressures (20, 40, 60 and 80 mmHg) were examined.Real-time quantitative PCR and Western blotting were operated to investigate the mRNA and protein expression levels of Epac 1 and PKCεin L5-S1 colonic-afferent dorsal root ganglions ( DRGs) .Results Compared with the control group , AWR scores in model group were in-creased at 40, 60 and 80 mmHg, while the pain threshold and maximal tolerance threshold were decreased (all P<0.05), which indicated the successful establishment of visceral hypersensitive model .Compared with the model group , AWR scores in the CE3F4 group were decreased at 40 and 60 mmHg, while the pain threshold and maximal tolerance threshold were increased (all P<0.05), meanwhile, the CE3F4 group was significantly higher than the model group (all P <0.05).Compared with the control group, the expression levels of Epac1 and PKCεat mRNA and protein in DRGs of the model group were increased (all P<0.05).Compared with the model group, the expression levels of Epac1 at mRNA and protein in DRGs of the CE3F4 group were not significantly different (all P>0.05), but the expression of PKCεat mRNA and protein levels in DRGs of the CE3F4 group were significantly decreased (all P<0.05).Conclusions Epac1 partici-pates in the regulation of visceral hypersensitivity and the mechanism may be related with the downstream activation of PKCε.
Keywords：irritable bowel syndromevisceral hypersensitivityEpac1protein kinase Cεrats
Publication Date：2016-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 9-12 )