Fig. 2.

Colonic hypersensitivity induced by acute irritation stress is ameliorated by RET kinase inhibition with motesanib or GSK3179106. (A) In comparison with rats given a saline enema (n = 8), those given an acetic acid enema and dosed with vehicle (n = 7) exhibit increased visceromotor response as evidenced by the increased number of abdominal contractions (mean ± S.E.M.) to colonic distension that is ameliorated when dosed orally with motesanib at 10 mg/kg (n = 7) for 3.5 days twice a day. **P < 0.01; ***P < 0.001; ****P < 0.0001 vehicle compared with saline or motesanib treatment, two-way RM-ANOVA, and Bonferroni’s post-test. (B) GSK3179106 dosed orally at 3 or 10 mg/kg (n = 7, all groups) for 3.5 days twice a day reduces the visceral motor response in comparison with rats given an acetic acid enema and dosed with vehicle. (C) GSK3179106 dosed orally at 10 mg/kg (n = 8) for 3.5 days twice a day had little effect on the visceral motor response in comparison with rats given a saline enema and dosed with vehicle (n = 7). *P < 0.05; ***P < 0.01; ****P < 0.0001 vehicle compared with GSK3179106 treatment, two-way RM-ANOVA, and Bonferroni’s post-test.