Abolished relationship between pancreatic HCO-3 secretion and arterial pH during carbonic anhydrase inhibition

After acetazolamide administration, CO2 hydration in pancreatic cells would be slow and might become a rate-limiting factor to pancreatic HCO-3 secretion. Correspondingly, pancreatic HCO-3 secretion-normally pH dependent-would become slow and pH-independent. However, acetazolamide would not be expected to interfere with the capacity of the secretory mechanism to generate a proton potential gradient between pancreatic cells and interstitial fluid. These predictions were examined in 5 anesthetized, secretion infused (2.7 C. U./kg b.wt. h-1) pigs. Pancreatic juice was collected from a catheter in the pancreatic duct. Arterial pH was varied through i.v. HCl and NaHCO3 infusions and CO2 addition to inspired air. Before acetazolamide, HCO-3 secretion varied with plasma pH and averaged 298 +/- 30 mumol/min at control arterial pH. Acetazolamide (150 mg/kg, i.v.) reduced HCO3 secretion to 84 +/- 12 mumol/min and rendered secretion independent of arterial pH between pH 7.6 and pH 7.0. It is concluded that acetazolamide imposes a pH-independent transport maximum on pancreatic HCO-3 secretion, but does not reduce the capacity of the secretory mechanism to sustain a proton potential gradient between cells and interstitial fluid.