Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

Figure 4 Electrical responses and ³H-mannitol fluxes of acid-injured porcine gastric mucosa. A: Porcine gastric mucosa exposed to acid (pH 1.5 for 90 min) exhibited a significant drop in transepithelial electrical resistance (TER), which was completely blocked by pretreatment with SPI-8811. In attempt to discern which chloride channel was involved in the gastro protective mechanism of SPI-8811, ClC-2 and cystic fibrosis transmembrane conductance regulator (CFTR) were inhibited. Addition of the ClC-2 inhibitor ZnCl₂ ameliorated the protective effect of SPI-8811 (TER, 100 Ω.cm²vs 80 Ω.cm²) whereas the CFTR inhibitor CFTR inhibitor 172 had no effect (TER, 100 Ω.cm²vs 100 Ω.cm²). Values represent mean ± SE, n = 6; ^aP < 0.05, ^bP < 0.01 vs all treatment groups; B: As an alternate measure of barrier permeability mucosal-to-serosal of ³H-mannitol flux were performed, and reveled a significant increase in mannitol permeability in acid injured tissues (^bP < 0.01). Pretreatment with SPI-8811 blocked the increase in ³H-mannitol flux caused by acid injury, whereas blockade of ClC-2 inhibitor ZnCl₂ block the protective effect of SPI-8811 (³H-mannitol flux, 0.04 μmol/L.cm²vs 0.12 μmol/L.cm², ^aP < 0.05) on permeability but CFTR inhibitor had no effect on the level of protective properties of SPI-8811 on permeability (³H-mannitol flux, 0.04 μmol/L.cm²vs 0.05 μmol/L.cm², ^bP < 0.01). Values represent mean ± SE, n = 6. NR: Normal Ringer’s.