Secretin stimulates ${\rm HCO}_{\rm 3}^{\rm - }$ and acetate efflux but not Na⁺/${\rm HCO}_{\rm 3}^{\rm - }$ uptake in rat pancreatic ducts

Abstract.

Pancreatic ducts secrete ${\rm HCO}_{\rm 3}^{\rm - }$ , but transport mechanisms are unresolved and possibly vary between species. Our aim was to study the intracellular pH (pH_i) regulation and thus H⁺/${\rm HCO}_{\rm 3}^{\rm - }$ transport in rat pancreatic ducts. Of particular interest was the Na⁺/${\rm HCO}_{\rm 3}^{\rm - }$ cotransporter, thought to be important in ${\rm HCO}_{\rm 3}^{\rm - }$ -transporting epithelia. pH_i was measured with BCECF in freshly isolated intralobular ducts. A reduction in extracellular Na⁺ concentration or application of HOE 694 (1 µM) decreased pH_i by 0.1 to 0.6 pH units, demonstrating Na⁺/H⁺ exchanger activity. A reduction in extracellular Cl^– concentration or addition of H₂DIDS (10 µM) increased pH_i by 0.1 to 0.5 pH units, demonstrating Cl^–/${\rm HCO}_{\rm 3}^{\rm - }$ (OH^–) exchanger activity. In experimental acidosis, extracellular ${\rm HCO}_{\rm 3}^{\rm - }$ /CO₂ buffer did not increase the rate of pH_i recovery, indicating that provision of ${\rm HCO}_{\rm 3}^{\rm - }$ by the Na⁺/${\rm HCO}_{\rm 3}^{\rm - }$ cotransporter was not apparent. Most importantly, Na⁺/${\rm HCO}_{\rm 3}^{\rm - }$ cotransport was not stimulated by secretin (1 nM). In contrast, in experimental alkalosis the pH_i recovery was increased in ${\rm HCO}_{\rm 3}^{\rm - }$ /CO₂ buffer, possibly due to Na⁺/${\rm HCO}_{\rm 3}^{\rm - }$ cotransport in the efflux mode. Secretin (1 nM) and carbachol (1 µM) stimulated ${\rm HCO}_{\rm 3}^{\rm - }$ efflux, which can account for the observed ${\rm HCO}_{\rm 3}^{\rm - }$ concentrations in rat pancreatic juice. Acetate and ${\rm HCO}_{\rm 3}^{\rm - }$ buffers were handled similarly, indicating similar transport mechanisms in pancreatic ducts.