HCO3- reduces paracellular permeability of guinea pig duodenal mucosa by a Ca2+ (prostaglandin)-dependent action.

The mechanism of HCO3(-)-induced decrease in electrical conductance (Gt) of guinea pig duodenal mucosa was investigated in vitro. Gt and unidirectional fluxes of mannitol (M), Na+, and Cl- were straightly correlated. In the presence of HCO3- (20 mM), elevating the bath concentration of Ca2+ from 0 to 1.2 mM caused decreases in Gt and Na+ fluxes by approximately 30%. Smaller reductions were found in the absence of HCO-3. With the addition of Ca2+, Gt and unidirectional fluxes were lower with than without HCO3-. In the latter condition, PM/PNa, PM/PCl, and PNa/PCl (P is permeability) were close or equal to ratios predictable from free solution diffusion coefficients; with HCO3-, ratios became different or more different and PM/PNa was reduced. Straightly correlated were conductivities of six differently composed HCO3(-)-free salines and Gt of tissues bathed therein. This correlation did not embrace HCO3- Ringer. The Gt effect of Ca2+ (HCO3- present) was mimicked by prostaglandin E2 and reduced (by approximately 40%) by Ca2+ channel blockers (diltiazem, gallopamil), cyclooxygenase inhibitors (meclofenamate, diclofenac), cytochalasin D, and trifluoperazine. We conclude that without HCO3-, paracellular solute flow occurs mainly via structures resembling a free-solution shunt; HCO3-, through an action made more efficient by Ca(2+)-mediated prostaglandin synthesis and possibly involving microfilaments, strengthens a discriminatory barrier.