Carbon monoxide contributes to the constipating effects of granisetron in rat colon

Figure 7 Effects of in vitro treatment with granisetron and zinc protoporphyrin and with granisetron and CORM-3 on rat colon contractile response to electrical field stimulation (EFS) and to acetylcholine (ACh). A: Co-incubation with granisetron (G) (3 μmol/L, 15 min) and zinc protoporphyrin (ZnPPIX) (10 μmol/L, 60 min) did not significantly modify the EFS-induced contraction compared to vehicle. ANOVA results: F_treatments = 0.43, df = 1/8, P = 0.53; F_frequencies = 55.35, df = 2/16, P < 0.0001; F_{treatments x frequencies} = 1.66, df = 2/16, P = 2; B: Co-incubation with G (3 μmol/L, 15 min) and ZnPPIX (10 μmol/L, 60 min) did not modify the myogenic contractile response to acetylcholine (ACh) (0.1-100 μmol/L) compared to vehicle. ANOVA results: F_treatments = 0.22, df = 1/8, P = 0.65; F_{concentrations} = 39.19, df = 3/24, P < 0.0001; F_{treatments x concentrations} = 4.06, df = 3/24, P = 0.02; C: Co-incubation with G (3 μmol/L, 15 min) and CORM-3 (C) (400 μmol/L) increased the contractile response to EFS at 5 and 10 Hz compared to vehicle. ANOVA results: F_treatments = 5.47, df = 3/19, P < 0.01; F_frequencies = 55.40, df = 2/38, P < 0.0001; F_{treatments x frequencies} = 3.05, df = 6/38, P = 0.04. G (3 μmol/L, 15 min) and C (400 μmol/L) vs vehicle at 5 Hz: ^aP = 0.007 and at 10 Hz: ^bP = 0.001; D: Co-incubation of G (3 μmol/L, 15 min) and C (400 μmol/L) increased the contractile response at ACh 10 and 100 μmol/L compared to vehicle. ANOVA results: F_treatments = 7.40, df = 3/19, P = 0.002; F_{concentrations} = 61.69, df = 3/57, P < 0.0001; F_{treatments x concentrations} = 3.55, df = 9/57, P = 0.027. G (3 μmol/L, 15 min) and C (400 μmol/L) compared to vehicle at ACh 10 μmol/L: ^cP = 0.001 and at ACh 100 μmol/L: ^dP = 0.001. Values are expressed as the mean ± SD of 6-8 experiments.