Effects of acid-base changes and carbonic anhydrase inhibition on pancreatic secretion

¹ Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

Pancreatic flow and HCO₃^– and Cl^– output were studied in dogs following 2 U/kg (i.v.) of secretin. Acetazolamide reduced flow and HCO₃^– output to half normal. HCl produced the same effect. NaHCO₃ increased flow and HCO₃^– output. CO₂ produced little change. Severe hyperventilation decreased flow and HCO₃^– output. Results are consistent with secretion dependent on the over-all reaction OH^– + CO₂ HCO₃^–, with both a carbonic-anhydrase catalyzed and an uncatalyzed component. Reduction of either reactant or of enzyme decreased output: increase of the reactants increased output. From in vitro kinetics and analysis of rates in vivo, the role of carbonic anhydrase may be assessed. About half of HCO₃^– output normally depends on the uncatalyzed reaction, and half on the catalyzed. In metabolic alterations, only the uncatalyzed component is affected. Pancreatic carbonic anhydrase is greatly in excess of that needed for the observed catalyzed rate in vivo. Correspondingly, reduction of output by acetazolamide occurs only when >99% of pancreatic carbonic anhydrase is inhibited. It is suggested that the rate-limiting event in pancreatic HCO₃^– secretion is transport of HCO₃^– from cell to duct.

Key Words: pancreas • enzyme • kinetics • acetazolamide • enzyme • inhibition

Submitted on February 8, 1963