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

Figure 8 Effects of in vitro treatment with granisetron, zinc protoporphyrin and N^G-nitro-L-Arginine and with granisetron, CORM-3 and L-NNA on rat colon contractile response to electrical field stimulation and to acetylcholine. A: Co-incubation with granisetron (G) (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) and N^G-nitro-L-Arginine (L-NNA) (100 μmol/L, 20 min) did not affect the electrical field stimulation (EFS)-induced contractile response compared to vehicle. ANOVA results: F_treatments = 0.08, df = 1/9, P = 0.79; F_frequencies = 24.89, df = 2/18, P < 0.0001; F_{treatments x frequencies} = 0.03, df = 2/18, P = 0.91; B: Co-incubation with G (3 μmol/L, 15 min), zinc protoporphyrin (ZnPPIX) (10 μmol/L, 60 min) and L-NNA (100 μmol/L, 20 min) did not affect the contractile response to acetylcholine (ACh) (0.1-100 μmol/L) compared to vehicle. ANOVA results: F_treatments = 0.03, df = 1/9, P = 0.87; F_{concentrations} = 45.18, df = 3/27, P < 0.0001; F_{treatments x concentrations} = 3.90, df = 3/27, P = 0.04; C: Co-incubation with G (3 μmol/L, 15 min), C (100-400 μmol/L) and L-NNA (100 μmol/L, 20 min) did not affect the EFS-induced contractile response compared to vehicle. ANOVA results: F_treatments = 0.83, df = 3/18, P = 0.49, F_frequencies = 25.51, df = 2/36, P < 0.0001; F_{treatments x frequencies} = 0.89, df = 6/36, P = 0.50; D: Co-incubation with G (3 μmol/L, 15 min), CORM-3 (C) (100-400 μmol/L) and L-NNA (100 μmol/L, 20 min) did not affect the contractile response to ACh (0.1-100 μmol/L) compared to vehicle. ANOVA results: F_treatments = 3.38, df = 3/17, P = 0.04, F_{concentrations} = 33.08, df = 3/57, P < 0.0001; F_{treatments x concentrations} = 1.47, df = 9/51, P = 0.25. Values are expressed as the mean ± SD of 6-8 experiments.