Fig. 4. IRBIT mediates the synergism between PKA and Ca²⁺ signaling pathways.

Panel (a) depict the synergistic activation of slc26a6 by 0.1μM forskolin and 0.1 and 0.3μM ATP. HeLa cells transfected with slc26a6 or slc26a6 and IRBIT(ΔPEST) were stimulated with ATP alone (close black circles), forskolin alone (open green circles) or with 0.1μM forskolin and the various concentrations of ATP (close red circles and open purple triangles). The results are the mea±s.e.m of 4–6 experiments. Panel (b) shows the synergistic activation of CFTR by 0.5μM forskolin and 3μM ATP. Maximal CFTR current is evoked by stimulation with 5 μM forskolin. Panels (c, d) show that IRBIT is required for synergistic activation of ductal fluid secretion. Fluid secretion in pancreatic ducts from wild-type and IRBIT^−/− mice was measured in sealed ducts in HCO₃⁻-buffered media and stimulated with 5μM forskolin or 30nM secretin (black circles), low concentration of 0.1μM forskolin or 2nM secretin (green circles), 1μM carbachol (blue circles) and the combination of 2nM secretin and 1μM carbachol (red circles).