Molecular Pharmacology, Vol 2, 144-157, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

A Study of Hepatic Carbonic Anhydrase

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

Dog and rat liver contain carbonic anhydrase in supernatant and particulate fractions. Hepatic bile of both species has higher HC0₃^- and lower Cl^- concentration than plasma. The enzyme in all fractions of dog liver was inhibited by unsubstituted aromatic sulfonamides at concentrations of 10^-6 to 10^-9 M. In vivo, administration of these drugs at doses which yield > 99% enzyme inhibition lowered biliary HCO₃^- and raised biliary Cl^- concentrations. Certain of the drugs were secreted by liver and concentrated in the bile of both species. Rat liver supernatant carbonic anhydrase was nearly refractory to sulfonamide inhibition in vitro; this is the first example of such lowered response in the animal kingdom. Biliary electrolytes in the rat were accordingly not altered by high doses of these sulfonamides.