P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome

Figure 3 Concentration selection of MRS2179. A: Treatment with the specific P2Y1R antagonist MRS2179 evoked a pain-related visceral motor response in AA rats upon colorectal distension. A significant decrease was observed at concentrations of 0.1 to 100 μmol/L at 2 to 168 h time points. MRS2179 at 100 μmol/L produced the most pronounced result. Maximal effects of MRS2179 were observed at 100 μmol/L at 72 h from a mean baseline AUC value of 1.587 ± 0.099 m.vs to 0.140 ± 0.089 m.vs; B: On naïve rats, MRS2179 at doses of 10 and 100 μmol/L was found to be effective after 48 h; C: On PBS rats, MRS2179 at doses of 10 and 100 μmol/L was found to be effective after 24 h; D and E: AUC of naïve, PBS and AA rats treated with MRS2179 at doses of 10 and 100 μmol/L. There were significant differences between AA rats and naïve/PBS rats at doses of 10 and 100 μmol/L, although differences between naïve and PBS rats were not significant for the two doses; F: AUC of AA rats treated with MRS2179 (from doses of 0.1 to 100 μmol/L) at 72 h time point. ^aP < 0.05, ^eP < 0.0001 vs the control group. AUC: Area under the electromyography curve; AA: acetic acid; EMG: Electromyography.