The effect of acetazolamide and carbonic anhydrase inhibition on erythrocyte 2,3-diphosphoglycerate content and metabolism

LL Rolf and LC Garg

Experiments were designed to test the hypothesis that the change in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) content which occurs when metabolic acidosis is induced by prolonged inhibition of carbonic anhydrase in vivo is the same as that which occurs with the induction of other types of metabolic acidosis states. 1) Thirteen-hour infusions of nondiuretic doses of a potent carbonic anhydrase inhibitor, acetazolamide (Diamox) did not alter erythrocyte 2,3-DPG levels in rats. 2) In vitro incubation of whole blood from rats for 10 days with high concentrations of two carbonic anhydrase inhibitors failed to alter the red cell content of 2,3-DPG. 3) Purified human carbonic anhydrase B had no phosphatase activity on 2,3-DPG and it appears unlikely that the enzyme hydrolyzes other phosphate esters of the erythrocyte which could indirectly alter 2,3-DPG content. 4) Acetazolamide administered in diuretic doses for 8 days to rats induced a metabolic acidosis which was accompanied by a decrease in erythrocyte 2,3-DPG. The change in 2,3-DPG content was similar to that produced by other methods of producing metabolic acidosis, namely NH4Cl treatment and nephrectomy. It appears that changes in 2,3-DPG content associated with effects of carbonic anhydrase inhibition can be ascribed to the metabolic acidosis resulting from the action of these drugs on the kidney.

Volume 193, Issue 2, pp. 639-646, 05/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics