Figure 10. Conceptual arrangement of mucus cells and enterocytes with components of Cl^– and HCO₃^– secretion and corresponding inhibitors.

In general, HCO₃^– is thought to be taken up across the basolateral membrane mainly via NBC, which is inhibited by DIDS. HCO₃^– exits the cell across the apical membrane, possibly via a CFTR-dependent Cl^–/HCO₃^– exchanger (also DIDS sensitive) or directly through the CFTR anion conductive channel that is inhibited by GlyH-101. Fluid secretion is dependent upon the uptake of Cl^– via the NKCC in the basolateral membrane, which is inhibited by bumetanide and on CFTR (or other Cl^– channels not shown) in the apical membrane. Thus, DIDS should block HCO₃^– secretion, and bumetanide should block fluid secretion. GlyH-101 is expected to inhibit both CFTR-dependent fluid and HCO₃^– secretion either directly by blocking CFTR conductance or indirectly by inhibiting a CFTR-dependent Cl^–/HCO₃^– exchanger (65). The diagram intentionally suggests close proximity of HCO₃^–-secreting enterocytes, with mucus-secreting goblet cells and possibly enterocytes as a means of maintaining ample HCO₃^– in the immediate environment of secreted mucin granules. In CF, defunct CFTR would starve the environment of HCO₃^–.